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Identification Taxonomy Ontology Physical properties Spectra Biological properties Concentrations Links References enzymes (17)transporters (4) Show 21 proteins XML

enzymes (17)transporters (4) Show 21 proteins

Record Information

Version

5.0

Status

Expected but not Quantified

Creation Date

2012-09-06 15:16:49 UTC

Update Date

2022-03-07 02:51:39 UTC

HMDB ID

HMDB0014542

Secondary Accession Numbers

HMDB14542

Metabolite Identification

Common Name

Sorafenib

Description

Sorafenib, also known as nexavar or sorafenib N-oxide, belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups. Sorafenib is a moderately basic compound (based on its pKa). Within humans, sorafenib participates in a number of enzymatic reactions. In particular, sorafenib and uridine diphosphate glucuronic acid can be converted into sorafenib β-D-glucuronide and uridine 5'-diphosphate; which is mediated by the enzyme UDP-glucuronosyltransferase 1-9. In addition, sorafenib can be converted into sorafenib N-oxide through its interaction with the enzyme cytochrome P450 3A4. In humans, sorafenib is involved in sorafenib metabolism pathway. Sorafenib is a potentially toxic compound. Desmoid tumor (aggressive fibromatosis) A study performed in 2011 showed that Sorafenib is active against aggressive fibromatosis. In a randomized, double-blind, phase II trial combining sorafenib with doxorubicin, the median time to progression was not significantly delayed compared with doxorubicin alone in patients with advanced hepatocellular carcinoma. At the current time sorafenib is indicated as a treatment for advanced renal cell carcinoma (RCC), unresectable hepatocellular carcinomas (HCC) and thyroid cancer. In Scotland the drug had already been refused authorization by the Scottish Medicines Consortium for use within NHS Scotland, for the same reason.

Structure

MOL 3D MOL SDF 3D SDF PDB 3D PDB SMILES InChI

398
  Mrv0541 02231214392D          

 32 34  0  0  0  0            999 V2000
    1.6500    3.0938    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    2.2540    3.9188    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    3.9041    3.9188    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    3.0791    4.7439    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    5.2224   -3.0938    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.7935    0.2063    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.0804   -2.2688    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.5080    1.4438    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.2224    0.2063    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.3659   -4.3313    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.7949   -3.5063    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.7935    1.8563    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0791    3.0938    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7935    2.6813    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2224   -0.6188    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0791    1.4438    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2224   -2.2688    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3645    2.6813    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9370   -1.0313    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5080   -1.0313    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3645    1.8563    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9370   -1.8563    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5080   -1.8563    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5080    0.6188    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0791    3.9188    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9370   -3.5063    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6515   -3.0938    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3659   -3.5063    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9370   -4.3313    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6515   -4.7439    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0804   -3.0938    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5094   -3.0938    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1 18  1  0  0  0  0
  2 25  1  0  0  0  0
  3 25  1  0  0  0  0
  4 25  1  0  0  0  0
  5 17  1  0  0  0  0
  5 26  1  0  0  0  0
  6 24  2  0  0  0  0
  7 31  2  0  0  0  0
  8 12  1  0  0  0  0
  8 24  1  0  0  0  0
  9 15  1  0  0  0  0
  9 24  1  0  0  0  0
 10 28  2  0  0  0  0
 10 30  1  0  0  0  0
 11 31  1  0  0  0  0
 11 32  1  0  0  0  0
 12 14  2  0  0  0  0
 12 16  1  0  0  0  0
 13 14  1  0  0  0  0
 13 18  2  0  0  0  0
 13 25  1  0  0  0  0
 15 19  2  0  0  0  0
 15 20  1  0  0  0  0
 16 21  2  0  0  0  0
 17 22  2  0  0  0  0
 17 23  1  0  0  0  0
 18 21  1  0  0  0  0
 19 22  1  0  0  0  0
 20 23  2  0  0  0  0
 26 27  2  0  0  0  0
 26 29  1  0  0  0  0
 27 28  1  0  0  0  0
 28 31  1  0  0  0  0
 29 30  2  0  0  0  0
M  END

HMDB0014542
     RDKit          3D
Sorafenib
 48 50  0  0  0  0  0  0  0  0999 V2000
    6.9409    2.8363   -1.6681 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2190    1.5732   -1.5126 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.6988    0.5938   -0.6175 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7549    0.8209    0.0442 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.0184   -0.6802   -0.4247 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8669   -1.0365   -1.0805 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2755   -2.2741   -0.8432 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1119   -2.5378   -1.5580 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.8752   -2.1735   -0.9910 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3172   -0.9429   -1.2015 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0800   -0.6066   -0.6220 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5876   -1.4966    0.1585 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8124   -1.2811    0.7595 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7142   -0.2419    0.4065 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3753    0.5213   -0.5138 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9519   -0.0730    1.0694 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.8937    0.9219    0.7878 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7711    1.9805   -0.0700 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.7734    2.9257   -0.2960 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.9549    2.7806    0.3876 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.2462    3.9494    0.1335 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -7.1214    1.7291    1.2617 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.4455    1.6525    1.9623 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.5259    0.5860    2.8057 F   0  0  0  0  0  0  0  0  0  0  0  0
   -9.4160    1.5295    0.9694 F   0  0  0  0  0  0  0  0  0  0  0  0
   -8.6047    2.8700    2.6218 F   0  0  0  0  0  0  0  0  0  0  0  0
   -6.1339    0.8265    1.4626 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0004   -2.7591    0.3662 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2080   -3.0728   -0.2059 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8166   -3.1758    0.0469 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9725   -2.7767    0.6825 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5395   -1.5872    0.4533 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.2144    3.6893   -1.5808 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.4049    2.8401   -2.6540 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.7246    2.9127   -0.8841 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.3582    1.4099   -2.0643 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.4267   -0.3370   -1.7858 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.8536   -0.2398   -1.8238 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2696    0.3898   -0.8348 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1408   -1.9219    1.5581 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1348   -0.7859    1.8398 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8338    2.0958   -0.6046 H   0  0  0  0  0  0  0  0  0  0  0  0
   -5.5563    3.7119   -0.9946 H   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2950    0.0120    2.1549 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4977   -3.5052    0.9845 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.6171   -4.0588   -0.0148 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.3384   -4.1273    0.2120 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.4233   -3.4670    1.3905 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  2  0
  3  5  1  0
  5  6  2  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
 11 12  2  0
 12 13  1  0
 13 14  1  0
 14 15  2  0
 14 16  1  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 20 22  1  0
 22 23  1  0
 23 24  1  0
 23 25  1  0
 23 26  1  0
 22 27  2  0
 12 28  1  0
 28 29  2  0
  7 30  2  0
 30 31  1  0
 31 32  2  0
 32  5  1  0
 29  9  1  0
 27 17  1  0
  1 33  1  0
  1 34  1  0
  1 35  1  0
  2 36  1  0
  6 37  1  0
 10 38  1  0
 11 39  1  0
 13 40  1  0
 16 41  1  0
 18 42  1  0
 19 43  1  0
 27 44  1  0
 28 45  1  0
 29 46  1  0
 30 47  1  0
 31 48  1  0
M  END

398
  Mrv0541 02231214392D          

 32 34  0  0  0  0            999 V2000
    1.6500    3.0938    0.0000 Cl  0  0  0  0  0  0  0  0  0  0  0  0
    2.2540    3.9188    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    3.9041    3.9188    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    3.0791    4.7439    0.0000 F   0  0  0  0  0  0  0  0  0  0  0  0
    5.2224   -3.0938    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    3.7935    0.2063    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    8.0804   -2.2688    0.0000 O   0  0  0  0  0  0  0  0  0  0  0  0
    4.5080    1.4438    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    5.2224    0.2063    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    7.3659   -4.3313    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    8.7949   -3.5063    0.0000 N   0  0  0  0  0  0  0  0  0  0  0  0
    3.7935    1.8563    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0791    3.0938    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.7935    2.6813    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2224   -0.6188    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0791    1.4438    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.2224   -2.2688    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3645    2.6813    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9370   -1.0313    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5080   -1.0313    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    2.3645    1.8563    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9370   -1.8563    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5080   -1.8563    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.5080    0.6188    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.0791    3.9188    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9370   -3.5063    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6515   -3.0938    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.3659   -3.5063    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9370   -4.3313    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.6515   -4.7439    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    8.0804   -3.0938    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
    9.5094   -3.0938    0.0000 C   0  0  0  0  0  0  0  0  0  0  0  0
  1 18  1  0  0  0  0
  2 25  1  0  0  0  0
  3 25  1  0  0  0  0
  4 25  1  0  0  0  0
  5 17  1  0  0  0  0
  5 26  1  0  0  0  0
  6 24  2  0  0  0  0
  7 31  2  0  0  0  0
  8 12  1  0  0  0  0
  8 24  1  0  0  0  0
  9 15  1  0  0  0  0
  9 24  1  0  0  0  0
 10 28  2  0  0  0  0
 10 30  1  0  0  0  0
 11 31  1  0  0  0  0
 11 32  1  0  0  0  0
 12 14  2  0  0  0  0
 12 16  1  0  0  0  0
 13 14  1  0  0  0  0
 13 18  2  0  0  0  0
 13 25  1  0  0  0  0
 15 19  2  0  0  0  0
 15 20  1  0  0  0  0
 16 21  2  0  0  0  0
 17 22  2  0  0  0  0
 17 23  1  0  0  0  0
 18 21  1  0  0  0  0
 19 22  1  0  0  0  0
 20 23  2  0  0  0  0
 26 27  2  0  0  0  0
 26 29  1  0  0  0  0
 27 28  1  0  0  0  0
 28 31  1  0  0  0  0
 29 30  2  0  0  0  0
M  END
> <DATABASE_ID>
HMDB0014542

> <DATABASE_NAME>
hmdb

> <SMILES>
CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1

> <INCHI_IDENTIFIER>
InChI=1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)

> <INCHI_KEY>
MLDQJTXFUGDVEO-UHFFFAOYSA-N

> <FORMULA>
C21H16ClF3N4O3

> <MOLECULAR_WEIGHT>
464.825

> <EXACT_MASS>
464.08630272

> <JCHEM_ACCEPTOR_COUNT>
3

> <JCHEM_AVERAGE_POLARIZABILITY>
41.10586489713454

> <JCHEM_BIOAVAILABILITY>
1

> <JCHEM_DONOR_COUNT>
3

> <JCHEM_FORMAL_CHARGE>
0

> <JCHEM_GHOSE_FILTER>
1

> <JCHEM_IUPAC>
4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide

> <ALOGPS_LOGP>
4.12

> <JCHEM_LOGP>
4.343329760666666

> <ALOGPS_LOGS>
-5.43

> <JCHEM_MDDR_LIKE_RULE>
1

> <JCHEM_NUMBER_OF_RINGS>
3

> <JCHEM_PHYSIOLOGICAL_CHARGE>
0

> <JCHEM_PKA>
13.992074435078546

> <JCHEM_PKA_STRONGEST_ACIDIC>
11.54979758623275

> <JCHEM_PKA_STRONGEST_BASIC>
2.0299195999719735

> <JCHEM_POLAR_SURFACE_AREA>
92.35000000000001

> <JCHEM_REFRACTIVITY>
114.51830000000001

> <JCHEM_ROTATABLE_BOND_COUNT>
6

> <JCHEM_RULE_OF_FIVE>
1

> <ALOGPS_SOLUBILITY>
1.71e-03 g/l

> <JCHEM_TRADITIONAL_IUPAC>
sorafenib

> <JCHEM_VEBER_RULE>
0

$$$$

HMDB0014542
     RDKit          3D
Sorafenib
 48 50  0  0  0  0  0  0  0  0999 V2000
    6.9409    2.8363   -1.6681 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2190    1.5732   -1.5126 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.6988    0.5938   -0.6175 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7549    0.8209    0.0442 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.0184   -0.6802   -0.4247 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8669   -1.0365   -1.0805 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2755   -2.2741   -0.8432 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1119   -2.5378   -1.5580 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.8752   -2.1735   -0.9910 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3172   -0.9429   -1.2015 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0800   -0.6066   -0.6220 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5876   -1.4966    0.1585 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8124   -1.2811    0.7595 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7142   -0.2419    0.4065 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3753    0.5213   -0.5138 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9519   -0.0730    1.0694 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.8937    0.9219    0.7878 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7711    1.9805   -0.0700 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.7734    2.9257   -0.2960 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.9549    2.7806    0.3876 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.2462    3.9494    0.1335 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -7.1214    1.7291    1.2617 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.4455    1.6525    1.9623 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.5259    0.5860    2.8057 F   0  0  0  0  0  0  0  0  0  0  0  0
   -9.4160    1.5295    0.9694 F   0  0  0  0  0  0  0  0  0  0  0  0
   -8.6047    2.8700    2.6218 F   0  0  0  0  0  0  0  0  0  0  0  0
   -6.1339    0.8265    1.4626 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0004   -2.7591    0.3662 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2080   -3.0728   -0.2059 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8166   -3.1758    0.0469 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9725   -2.7767    0.6825 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5395   -1.5872    0.4533 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.2144    3.6893   -1.5808 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.4049    2.8401   -2.6540 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.7246    2.9127   -0.8841 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.3582    1.4099   -2.0643 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.4267   -0.3370   -1.7858 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.8536   -0.2398   -1.8238 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2696    0.3898   -0.8348 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1408   -1.9219    1.5581 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1348   -0.7859    1.8398 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8338    2.0958   -0.6046 H   0  0  0  0  0  0  0  0  0  0  0  0
   -5.5563    3.7119   -0.9946 H   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2950    0.0120    2.1549 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4977   -3.5052    0.9845 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.6171   -4.0588   -0.0148 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.3384   -4.1273    0.2120 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.4233   -3.4670    1.3905 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  2  0
  3  5  1  0
  5  6  2  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
 11 12  2  0
 12 13  1  0
 13 14  1  0
 14 15  2  0
 14 16  1  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 20 22  1  0
 22 23  1  0
 23 24  1  0
 23 25  1  0
 23 26  1  0
 22 27  2  0
 12 28  1  0
 28 29  2  0
  7 30  2  0
 30 31  1  0
 31 32  2  0
 32  5  1  0
 29  9  1  0
 27 17  1  0
  1 33  1  0
  1 34  1  0
  1 35  1  0
  2 36  1  0
  6 37  1  0
 10 38  1  0
 11 39  1  0
 13 40  1  0
 16 41  1  0
 18 42  1  0
 19 43  1  0
 27 44  1  0
 28 45  1  0
 29 46  1  0
 30 47  1  0
 31 48  1  0
M  END

HEADER    PROTEIN                                 23-FEB-12   NONE
TITLE     NULL                                                        
COMPND    MOLECULE: 398                                               
SOURCE    NULL                                                        
KEYWDS    NULL                                                        
EXPDTA    NULL                                                        
AUTHOR    Marvin                                                      
REVDAT   1   23-FEB-12         0                                  
HETATM    1 Cl   UNK     0       3.080   5.775   0.000  0.00  0.00          Cl+0
HETATM    2  F   UNK     0       4.207   7.315   0.000  0.00  0.00           F+0
HETATM    3  F   UNK     0       7.288   7.315   0.000  0.00  0.00           F+0
HETATM    4  F   UNK     0       5.748   8.855   0.000  0.00  0.00           F+0
HETATM    5  O   UNK     0       9.748  -5.775   0.000  0.00  0.00           O+0
HETATM    6  O   UNK     0       7.081   0.385   0.000  0.00  0.00           O+0
HETATM    7  O   UNK     0      15.083  -4.235   0.000  0.00  0.00           O+0
HETATM    8  N   UNK     0       8.415   2.695   0.000  0.00  0.00           N+0
HETATM    9  N   UNK     0       9.748   0.385   0.000  0.00  0.00           N+0
HETATM   10  N   UNK     0      13.750  -8.085   0.000  0.00  0.00           N+0
HETATM   11  N   UNK     0      16.417  -6.545   0.000  0.00  0.00           N+0
HETATM   12  C   UNK     0       7.081   3.465   0.000  0.00  0.00           C+0
HETATM   13  C   UNK     0       5.748   5.775   0.000  0.00  0.00           C+0
HETATM   14  C   UNK     0       7.081   5.005   0.000  0.00  0.00           C+0
HETATM   15  C   UNK     0       9.748  -1.155   0.000  0.00  0.00           C+0
HETATM   16  C   UNK     0       5.748   2.695   0.000  0.00  0.00           C+0
HETATM   17  C   UNK     0       9.748  -4.235   0.000  0.00  0.00           C+0
HETATM   18  C   UNK     0       4.414   5.005   0.000  0.00  0.00           C+0
HETATM   19  C   UNK     0      11.082  -1.925   0.000  0.00  0.00           C+0
HETATM   20  C   UNK     0       8.415  -1.925   0.000  0.00  0.00           C+0
HETATM   21  C   UNK     0       4.414   3.465   0.000  0.00  0.00           C+0
HETATM   22  C   UNK     0      11.082  -3.465   0.000  0.00  0.00           C+0
HETATM   23  C   UNK     0       8.415  -3.465   0.000  0.00  0.00           C+0
HETATM   24  C   UNK     0       8.415   1.155   0.000  0.00  0.00           C+0
HETATM   25  C   UNK     0       5.748   7.315   0.000  0.00  0.00           C+0
HETATM   26  C   UNK     0      11.082  -6.545   0.000  0.00  0.00           C+0
HETATM   27  C   UNK     0      12.416  -5.775   0.000  0.00  0.00           C+0
HETATM   28  C   UNK     0      13.750  -6.545   0.000  0.00  0.00           C+0
HETATM   29  C   UNK     0      11.082  -8.085   0.000  0.00  0.00           C+0
HETATM   30  C   UNK     0      12.416  -8.855   0.000  0.00  0.00           C+0
HETATM   31  C   UNK     0      15.083  -5.775   0.000  0.00  0.00           C+0
HETATM   32  C   UNK     0      17.751  -5.775   0.000  0.00  0.00           C+0
CONECT    1   18                                                            
CONECT    2   25                                                            
CONECT    3   25                                                            
CONECT    4   25                                                            
CONECT    5   17   26                                                       
CONECT    6   24                                                            
CONECT    7   31                                                            
CONECT    8   12   24                                                       
CONECT    9   15   24                                                       
CONECT   10   28   30                                                       
CONECT   11   31   32                                                       
CONECT   12    8   14   16                                                  
CONECT   13   14   18   25                                                  
CONECT   14   12   13                                                       
CONECT   15    9   19   20                                                  
CONECT   16   12   21                                                       
CONECT   17    5   22   23                                                  
CONECT   18    1   13   21                                                  
CONECT   19   15   22                                                       
CONECT   20   15   23                                                       
CONECT   21   16   18                                                       
CONECT   22   17   19                                                       
CONECT   23   17   20                                                       
CONECT   24    6    8    9                                                  
CONECT   25    2    3    4   13                                             
CONECT   26    5   27   29                                                  
CONECT   27   26   28                                                       
CONECT   28   10   27   31                                                  
CONECT   29   26   30                                                       
CONECT   30   10   29                                                       
CONECT   31    7   11   28                                                  
CONECT   32   11                                                            
MASTER        0    0    0    0    0    0    0    0   32    0   68    0
END

COMPND    HMDB0014542
HETATM    1  C1  UNL     1       6.941   2.836  -1.668  1.00  0.00           C  
HETATM    2  N1  UNL     1       6.219   1.573  -1.513  1.00  0.00           N  
HETATM    3  C2  UNL     1       6.699   0.594  -0.618  1.00  0.00           C  
HETATM    4  O1  UNL     1       7.755   0.821   0.044  1.00  0.00           O  
HETATM    5  C3  UNL     1       6.018  -0.680  -0.425  1.00  0.00           C  
HETATM    6  C4  UNL     1       4.867  -1.037  -1.080  1.00  0.00           C  
HETATM    7  C5  UNL     1       4.276  -2.274  -0.843  1.00  0.00           C  
HETATM    8  O2  UNL     1       3.112  -2.538  -1.558  1.00  0.00           O  
HETATM    9  C6  UNL     1       1.875  -2.174  -0.991  1.00  0.00           C  
HETATM   10  C7  UNL     1       1.317  -0.943  -1.201  1.00  0.00           C  
HETATM   11  C8  UNL     1       0.080  -0.607  -0.622  1.00  0.00           C  
HETATM   12  C9  UNL     1      -0.588  -1.497   0.159  1.00  0.00           C  
HETATM   13  N2  UNL     1      -1.812  -1.281   0.760  1.00  0.00           N  
HETATM   14  C10 UNL     1      -2.714  -0.242   0.406  1.00  0.00           C  
HETATM   15  O3  UNL     1      -2.375   0.521  -0.514  1.00  0.00           O  
HETATM   16  N3  UNL     1      -3.952  -0.073   1.069  1.00  0.00           N  
HETATM   17  C11 UNL     1      -4.894   0.922   0.788  1.00  0.00           C  
HETATM   18  C12 UNL     1      -4.771   1.980  -0.070  1.00  0.00           C  
HETATM   19  C13 UNL     1      -5.773   2.926  -0.296  1.00  0.00           C  
HETATM   20  C14 UNL     1      -6.955   2.781   0.388  1.00  0.00           C  
HETATM   21 CL1  UNL     1      -8.246   3.949   0.134  1.00  0.00          CL  
HETATM   22  C15 UNL     1      -7.121   1.729   1.262  1.00  0.00           C  
HETATM   23  C16 UNL     1      -8.446   1.653   1.962  1.00  0.00           C  
HETATM   24  F1  UNL     1      -8.526   0.586   2.806  1.00  0.00           F  
HETATM   25  F2  UNL     1      -9.416   1.530   0.969  1.00  0.00           F  
HETATM   26  F3  UNL     1      -8.605   2.870   2.622  1.00  0.00           F  
HETATM   27  C17 UNL     1      -6.134   0.827   1.463  1.00  0.00           C  
HETATM   28  C18 UNL     1      -0.000  -2.759   0.366  1.00  0.00           C  
HETATM   29  C19 UNL     1       1.208  -3.073  -0.206  1.00  0.00           C  
HETATM   30  C20 UNL     1       4.817  -3.176   0.047  1.00  0.00           C  
HETATM   31  C21 UNL     1       5.972  -2.777   0.682  1.00  0.00           C  
HETATM   32  N4  UNL     1       6.539  -1.587   0.453  1.00  0.00           N  
HETATM   33  H1  UNL     1       6.214   3.689  -1.581  1.00  0.00           H  
HETATM   34  H2  UNL     1       7.405   2.840  -2.654  1.00  0.00           H  
HETATM   35  H3  UNL     1       7.725   2.913  -0.884  1.00  0.00           H  
HETATM   36  H4  UNL     1       5.358   1.410  -2.064  1.00  0.00           H  
HETATM   37  H5  UNL     1       4.427  -0.337  -1.786  1.00  0.00           H  
HETATM   38  H6  UNL     1       1.854  -0.240  -1.824  1.00  0.00           H  
HETATM   39  H7  UNL     1      -0.270   0.390  -0.835  1.00  0.00           H  
HETATM   40  H8  UNL     1      -2.141  -1.922   1.558  1.00  0.00           H  
HETATM   41  H9  UNL     1      -4.135  -0.786   1.840  1.00  0.00           H  
HETATM   42  H10 UNL     1      -3.834   2.096  -0.605  1.00  0.00           H  
HETATM   43  H11 UNL     1      -5.556   3.712  -0.995  1.00  0.00           H  
HETATM   44  H12 UNL     1      -6.295   0.012   2.155  1.00  0.00           H  
HETATM   45  H13 UNL     1      -0.498  -3.505   0.984  1.00  0.00           H  
HETATM   46  H14 UNL     1       1.617  -4.059  -0.015  1.00  0.00           H  
HETATM   47  H15 UNL     1       4.338  -4.127   0.212  1.00  0.00           H  
HETATM   48  H16 UNL     1       6.423  -3.467   1.391  1.00  0.00           H  
CONECT    1    2   33   34   35
CONECT    2    3   36
CONECT    3    4    4    5
CONECT    5    6    6   32
CONECT    6    7   37
CONECT    7    8   30   30
CONECT    8    9
CONECT    9   10   10   29
CONECT   10   11   38
CONECT   11   12   12   39
CONECT   12   13   28
CONECT   13   14   40
CONECT   14   15   15   16
CONECT   16   17   41
CONECT   17   18   18   27
CONECT   18   19   42
CONECT   19   20   20   43
CONECT   20   21   22
CONECT   22   23   27   27
CONECT   23   24   25   26
CONECT   27   44
CONECT   28   29   29   45
CONECT   29   46
CONECT   30   31   47
CONECT   31   32   32   48
END

HMDB0014542
     RDKit          3D
Sorafenib
 48 50  0  0  0  0  0  0  0  0999 V2000
    6.9409    2.8363   -1.6681 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.2190    1.5732   -1.5126 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.6988    0.5938   -0.6175 C   0  0  0  0  0  0  0  0  0  0  0  0
    7.7549    0.8209    0.0442 O   0  0  0  0  0  0  0  0  0  0  0  0
    6.0184   -0.6802   -0.4247 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8669   -1.0365   -1.0805 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.2755   -2.2741   -0.8432 C   0  0  0  0  0  0  0  0  0  0  0  0
    3.1119   -2.5378   -1.5580 O   0  0  0  0  0  0  0  0  0  0  0  0
    1.8752   -2.1735   -0.9910 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.3172   -0.9429   -1.2015 C   0  0  0  0  0  0  0  0  0  0  0  0
    0.0800   -0.6066   -0.6220 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.5876   -1.4966    0.1585 C   0  0  0  0  0  0  0  0  0  0  0  0
   -1.8124   -1.2811    0.7595 N   0  0  0  0  0  0  0  0  0  0  0  0
   -2.7142   -0.2419    0.4065 C   0  0  0  0  0  0  0  0  0  0  0  0
   -2.3753    0.5213   -0.5138 O   0  0  0  0  0  0  0  0  0  0  0  0
   -3.9519   -0.0730    1.0694 N   0  0  0  0  0  0  0  0  0  0  0  0
   -4.8937    0.9219    0.7878 C   0  0  0  0  0  0  0  0  0  0  0  0
   -4.7711    1.9805   -0.0700 C   0  0  0  0  0  0  0  0  0  0  0  0
   -5.7734    2.9257   -0.2960 C   0  0  0  0  0  0  0  0  0  0  0  0
   -6.9549    2.7806    0.3876 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.2462    3.9494    0.1335 Cl  0  0  0  0  0  0  0  0  0  0  0  0
   -7.1214    1.7291    1.2617 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.4455    1.6525    1.9623 C   0  0  0  0  0  0  0  0  0  0  0  0
   -8.5259    0.5860    2.8057 F   0  0  0  0  0  0  0  0  0  0  0  0
   -9.4160    1.5295    0.9694 F   0  0  0  0  0  0  0  0  0  0  0  0
   -8.6047    2.8700    2.6218 F   0  0  0  0  0  0  0  0  0  0  0  0
   -6.1339    0.8265    1.4626 C   0  0  0  0  0  0  0  0  0  0  0  0
   -0.0004   -2.7591    0.3662 C   0  0  0  0  0  0  0  0  0  0  0  0
    1.2080   -3.0728   -0.2059 C   0  0  0  0  0  0  0  0  0  0  0  0
    4.8166   -3.1758    0.0469 C   0  0  0  0  0  0  0  0  0  0  0  0
    5.9725   -2.7767    0.6825 C   0  0  0  0  0  0  0  0  0  0  0  0
    6.5395   -1.5872    0.4533 N   0  0  0  0  0  0  0  0  0  0  0  0
    6.2144    3.6893   -1.5808 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.4049    2.8401   -2.6540 H   0  0  0  0  0  0  0  0  0  0  0  0
    7.7246    2.9127   -0.8841 H   0  0  0  0  0  0  0  0  0  0  0  0
    5.3582    1.4099   -2.0643 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.4267   -0.3370   -1.7858 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.8536   -0.2398   -1.8238 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.2696    0.3898   -0.8348 H   0  0  0  0  0  0  0  0  0  0  0  0
   -2.1408   -1.9219    1.5581 H   0  0  0  0  0  0  0  0  0  0  0  0
   -4.1348   -0.7859    1.8398 H   0  0  0  0  0  0  0  0  0  0  0  0
   -3.8338    2.0958   -0.6046 H   0  0  0  0  0  0  0  0  0  0  0  0
   -5.5563    3.7119   -0.9946 H   0  0  0  0  0  0  0  0  0  0  0  0
   -6.2950    0.0120    2.1549 H   0  0  0  0  0  0  0  0  0  0  0  0
   -0.4977   -3.5052    0.9845 H   0  0  0  0  0  0  0  0  0  0  0  0
    1.6171   -4.0588   -0.0148 H   0  0  0  0  0  0  0  0  0  0  0  0
    4.3384   -4.1273    0.2120 H   0  0  0  0  0  0  0  0  0  0  0  0
    6.4233   -3.4670    1.3905 H   0  0  0  0  0  0  0  0  0  0  0  0
  1  2  1  0
  2  3  1  0
  3  4  2  0
  3  5  1  0
  5  6  2  0
  6  7  1  0
  7  8  1  0
  8  9  1  0
  9 10  2  0
 10 11  1  0
 11 12  2  0
 12 13  1  0
 13 14  1  0
 14 15  2  0
 14 16  1  0
 16 17  1  0
 17 18  2  0
 18 19  1  0
 19 20  2  0
 20 21  1  0
 20 22  1  0
 22 23  1  0
 23 24  1  0
 23 25  1  0
 23 26  1  0
 22 27  2  0
 12 28  1  0
 28 29  2  0
  7 30  2  0
 30 31  1  0
 31 32  2  0
 32  5  1  0
 29  9  1  0
 27 17  1  0
  1 33  1  0
  1 34  1  0
  1 35  1  0
  2 36  1  0
  6 37  1  0
 10 38  1  0
 11 39  1  0
 13 40  1  0
 16 41  1  0
 18 42  1  0
 19 43  1  0
 27 44  1  0
 28 45  1  0
 29 46  1  0
 30 47  1  0
 31 48  1  0
M  END

View in JSmol View Stereo Labels

Synonyms

Value	Source
4-(4-((((4-Chloro-3-(trifluoromethyl)phenyl)amino)carbonyl)amino)phenoxy)-N-methyl-2-pyridinecarboxamide	ChEBI
N-(4-Chloro-3-(trifluoromethyl)phenyl)-n'-(4-(2-(N-methylcarbamoyl)-4-pyridyloxy)phenyl)urea	ChEBI
Sorafenibum	ChEBI
Sorafenib tosylate	HMDB
4-(4-(3-(4-Chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxyllic acid methyamide-4-methylbenzenesulfonate	HMDB
Nexavar	HMDB
Sorafenib N-oxide	HMDB
Sorafenib N oxide	HMDB
4-(4-(3-(4-Chloro-3-trifluoromethylphenyl)ureido)phenoxy)pyridine-2-carboxylic acid methyamide-4-methylbenzenesulfonate	HMDB

Chemical Formula

C₂₁H₁₆ClF₃N₄O₃

Average Molecular Weight

464.825

Monoisotopic Molecular Weight

464.08630272

IUPAC Name

4-[4-({[4-chloro-3-(trifluoromethyl)phenyl]carbamoyl}amino)phenoxy]-N-methylpyridine-2-carboxamide

Traditional Name

sorafenib

CAS Registry Number

284461-73-0

SMILES

CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1

InChI Identifier

InChI=1S/C21H16ClF3N4O3/c1-26-19(30)18-11-15(8-9-27-18)32-14-5-2-12(3-6-14)28-20(31)29-13-4-7-17(22)16(10-13)21(23,24)25/h2-11H,1H3,(H,26,30)(H2,28,29,31)

InChI Key

MLDQJTXFUGDVEO-UHFFFAOYSA-N

Chemical Taxonomy

Description

Belongs to the class of organic compounds known as diarylethers. These are organic compounds containing the dialkyl ether functional group, with the formula ROR', where R and R' are aryl groups.

Kingdom

Organic compounds

Super Class

Organic oxygen compounds

Class

Organooxygen compounds

Sub Class

Ethers

Direct Parent

Diarylethers

Alternative Parents

Substituents

Diaryl ether
Trifluoromethylbenzene
N-phenylurea
Pyridine carboxylic acid or derivatives
Pyridinecarboxamide
2-heteroaryl carboxamide
Phenoxy compound
Phenol ether
Halobenzene
Chlorobenzene
Benzenoid
Pyridine
Monocyclic benzene moiety
Aryl halide
Aryl chloride
Heteroaromatic compound
Urea
Secondary carboxylic acid amide
Carbonic acid derivative
Carboxamide group
Azacycle
Organoheterocyclic compound
Carboxylic acid derivative
Organic nitrogen compound
Organopnictogen compound
Organic oxide
Hydrocarbon derivative
Organonitrogen compound
Organofluoride
Organochloride
Organohalogen compound
Carbonyl group
Alkyl halide
Alkyl fluoride
Aromatic heteromonocyclic compound

Molecular Framework

Aromatic heteromonocyclic compounds

External Descriptors

aromatic ether (CHEBI:50924 )
ureas (CHEBI:50924 )
monochlorobenzenes (CHEBI:50924 )
(trifluoromethyl)benzenes (CHEBI:50924 )
pyridinecarboxamide (CHEBI:50924 )

Ontology

Physiological effect

Not Available

Disposition

Biological location

Non-excretory biofluid

Biofluid or Excreta

Blood (PMID: 21059682)

Excreta

Biofluid or Excreta

Urine (PMID: 21059682)

Cellular substructure

Cytoplasm (HMDB: HMDB0014542)
Membrane (HMDB: HMDB0014542)

Source

Exogenous

Exogenous (HMDB: HMDB0014542)

Process

Naturally occurring process

Biological process

Biochemical pathway

Metabolic pathway

Sorafenib Metabolism Pathway (PathBank: SMP0000648)

Role

Industrial application

Antineoplastic agent (HMDB: HMDB0014542)

Biological role

Modulator

Inhibitor

EC 2.7.11.1 (non-specific serine/threonine protein kinase) inhibitor (HMDB: HMDB0014542)

Enzyme inhibitor

Tyrosine-kinase inhibitor (HMDB: HMDB0014542)

Antiangiogenic (HMDB: HMDB0014542)

Physical Properties

State

Solid

Experimental Molecular Properties

Property	Value	Reference
Melting Point	Not Available	Not Available
Boiling Point	Not Available	Not Available
Water Solubility	0.0017 g/L	Not Available
LogP	3.8	Not Available

Experimental Chromatographic Properties

Not Available

Predicted Molecular Properties

Property	Value	Source
Water Solubility	0.0017 g/L	ALOGPS
logP	4.12	ALOGPS
logP	4.34	ChemAxon
logS	-5.4	ALOGPS
pKa (Strongest Acidic)	11.55	ChemAxon
pKa (Strongest Basic)	2.03	ChemAxon
Physiological Charge	0	ChemAxon
Hydrogen Acceptor Count	3	ChemAxon
Hydrogen Donor Count	3	ChemAxon
Polar Surface Area	92.35 Å²	ChemAxon
Rotatable Bond Count	6	ChemAxon
Refractivity	114.52 m³·mol⁻¹	ChemAxon
Polarizability	41.11 Å³	ChemAxon
Number of Rings	3	ChemAxon
Bioavailability	Yes	ChemAxon
Rule of Five	Yes	ChemAxon
Ghose Filter	Yes	ChemAxon
Veber's Rule	No	ChemAxon
MDDR-like Rule	Yes	ChemAxon

Predicted Chromatographic Properties

Predicted Collision Cross Sections

Predictor	Adduct Type	CCS Value (Å²)	Reference
DeepCCS	[M+H]+	204.137	30932474
DeepCCS	[M-H]-	201.742	30932474
DeepCCS	[M-2H]-	234.625	30932474
DeepCCS	[M+Na]+	210.07	30932474
AllCCS	[M+H]+	202.4	32859911
AllCCS	[M+H-H2O]+	200.2	32859911
AllCCS	[M+NH4]+	204.5	32859911
AllCCS	[M+Na]+	205.1	32859911
AllCCS	[M-H]-	193.5	32859911
AllCCS	[M+Na-2H]-	193.0	32859911
AllCCS	[M+HCOO]-	192.7	32859911

Predicted Retention Times

Underivatized

Chromatographic Method	Retention Time	Reference
Measured using a Waters Acquity ultraperformance liquid chromatography (UPLC) ethylene-bridged hybrid (BEH) C18 column (100 mm × 2.1 mm; 1.7 μmparticle diameter). Predicted by Afia on May 17, 2022. Predicted by Afia on May 17, 2022.	6.6 minutes	32390414
Predicted by Siyang on May 30, 2022	15.0031 minutes	33406817
Predicted by Siyang using ReTip algorithm on June 8, 2022	0.9 minutes	32390414
Fem_Long = Waters ACQUITY UPLC HSS T3 C18 with Water:MeOH and 0.1% Formic Acid	2538.6 seconds	40023050
Fem_Lipids = Ascentis Express C18 with (60:40 water:ACN):(90:10 IPA:ACN) and 10mM NH4COOH + 0.1% Formic Acid	326.7 seconds	40023050
Life_Old = Waters ACQUITY UPLC BEH C18 with Water:(20:80 acetone:ACN) and 0.1% Formic Acid	178.9 seconds	40023050
Life_New = RP Waters ACQUITY UPLC HSS T3 C18 with Water:(30:70 MeOH:ACN) and 0.1% Formic Acid	195.1 seconds	40023050
RIKEN = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	140.6 seconds	40023050
Eawag_XBridgeC18 = XBridge C18 3.5u 2.1x50 mm with Water:MeOH and 0.1% Formic Acid	544.6 seconds	40023050
BfG_NTS_RP1 =Agilent Zorbax Eclipse Plus C18 (2.1 mm x 150 mm, 3.5 um) with Water:ACN and 0.1% Formic Acid	649.6 seconds	40023050
HILIC_BDD_2 = Merck SeQuant ZIC-HILIC with ACN(0.1% formic acid):water(16 mM ammonium formate)	80.6 seconds	40023050
UniToyama_Atlantis = RP Waters Atlantis T3 (2.1 x 150 mm, 5 um) with ACN:Water and 0.1% Formic Acid	1240.6 seconds	40023050
BDD_C18 = Hypersil Gold 1.9µm C18 with Water:ACN and 0.1% Formic Acid	498.5 seconds	40023050
UFZ_Phenomenex = Kinetex Core-Shell C18 2.6 um, 3.0 x 100 mm, Phenomenex with Water:MeOH and 0.1% Formic Acid	1475.1 seconds	40023050
SNU_RIKEN_POS = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	434.5 seconds	40023050
RPMMFDA = Waters ACQUITY UPLC BEH C18 with Water:ACN and 0.1% Formic Acid	393.7 seconds	40023050
MTBLS87 = Merck SeQuant ZIC-pHILIC column with ACN:Water and :ammonium carbonate	269.0 seconds	40023050
KI_GIAR_zic_HILIC_pH2_7 = Merck SeQuant ZIC-HILIC with ACN:Water and 0.1% FA	99.7 seconds	40023050
Meister zic-pHILIC pH9.3 = Merck SeQuant ZIC-pHILIC column with ACN:Water 5mM NH4Ac pH9.3 and 5mM ammonium acetate in water	13.0 seconds	40023050

Predicted Kovats Retention Indices

Underivatized

Metabolite	SMILES	Kovats RI Value	Column Type	Reference
Sorafenib	CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1	4631.9	Standard polar	33892256
Sorafenib	CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1	3284.6	Standard non polar	33892256
Sorafenib	CNC(=O)C1=NC=CC(OC2=CC=C(NC(=O)NC3=CC(=C(Cl)C=C3)C(F)(F)F)C=C2)=C1	3969.9	Semi standard non polar	33892256

Derivatized

Derivative Name / Structure	SMILES	Kovats RI Value	Column Type	Reference
Sorafenib,1TMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)C=C2)=CC=N1)[Si](C)(C)C	3725.5	Semi standard non polar	33892256
Sorafenib,1TMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)C=C2)=CC=N1)[Si](C)(C)C	3136.6	Standard non polar	33892256
Sorafenib,1TMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)C=C2)=CC=N1)[Si](C)(C)C	4383.9	Standard polar	33892256
Sorafenib,1TMS,isomer #2	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1	3500.4	Semi standard non polar	33892256
Sorafenib,1TMS,isomer #2	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1	2978.0	Standard non polar	33892256
Sorafenib,1TMS,isomer #2	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1	4497.7	Standard polar	33892256
Sorafenib,1TMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1	3507.6	Semi standard non polar	33892256
Sorafenib,1TMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1	2968.8	Standard non polar	33892256
Sorafenib,1TMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1	4584.6	Standard polar	33892256
Sorafenib,2TMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1)[Si](C)(C)C	3506.2	Semi standard non polar	33892256
Sorafenib,2TMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1)[Si](C)(C)C	2906.2	Standard non polar	33892256
Sorafenib,2TMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1)[Si](C)(C)C	3942.5	Standard polar	33892256
Sorafenib,2TMS,isomer #2	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1)[Si](C)(C)C	3504.2	Semi standard non polar	33892256
Sorafenib,2TMS,isomer #2	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1)[Si](C)(C)C	2879.5	Standard non polar	33892256
Sorafenib,2TMS,isomer #2	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)C=C2)=CC=N1)[Si](C)(C)C	4030.9	Standard polar	33892256
Sorafenib,2TMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)[Si](C)(C)C)C=C2)=CC=N1	3331.6	Semi standard non polar	33892256
Sorafenib,2TMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)[Si](C)(C)C)C=C2)=CC=N1	2862.5	Standard non polar	33892256
Sorafenib,2TMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)[Si](C)(C)C)C=C2)=CC=N1	4122.3	Standard polar	33892256
Sorafenib,3TMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)[Si](C)(C)C)C=C2)=CC=N1)[Si](C)(C)C	3350.7	Semi standard non polar	33892256
Sorafenib,3TMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)[Si](C)(C)C)C=C2)=CC=N1)[Si](C)(C)C	2837.8	Standard non polar	33892256
Sorafenib,3TMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C)[Si](C)(C)C)C=C2)=CC=N1)[Si](C)(C)C	3691.1	Standard polar	33892256
Sorafenib,1TBDMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	3967.5	Semi standard non polar	33892256
Sorafenib,1TBDMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	3276.1	Standard non polar	33892256
Sorafenib,1TBDMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	4418.4	Standard polar	33892256
Sorafenib,1TBDMS,isomer #2	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1	3713.5	Semi standard non polar	33892256
Sorafenib,1TBDMS,isomer #2	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1	3137.3	Standard non polar	33892256
Sorafenib,1TBDMS,isomer #2	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1	4477.0	Standard polar	33892256
Sorafenib,1TBDMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1	3727.2	Semi standard non polar	33892256
Sorafenib,1TBDMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1	3117.7	Standard non polar	33892256
Sorafenib,1TBDMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1	4562.8	Standard polar	33892256
Sorafenib,2TBDMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	3958.0	Semi standard non polar	33892256
Sorafenib,2TBDMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	3193.1	Standard non polar	33892256
Sorafenib,2TBDMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)NC3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	4048.3	Standard polar	33892256
Sorafenib,2TBDMS,isomer #2	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	3973.9	Semi standard non polar	33892256
Sorafenib,2TBDMS,isomer #2	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	3182.1	Standard non polar	33892256
Sorafenib,2TBDMS,isomer #2	CN(C(=O)C1=CC(OC2=CC=C(NC(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	4136.5	Standard polar	33892256
Sorafenib,2TBDMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1	3761.8	Semi standard non polar	33892256
Sorafenib,2TBDMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1	3167.4	Standard non polar	33892256
Sorafenib,2TBDMS,isomer #3	CNC(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1	4208.0	Standard polar	33892256
Sorafenib,3TBDMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	4004.9	Semi standard non polar	33892256
Sorafenib,3TBDMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	3292.9	Standard non polar	33892256
Sorafenib,3TBDMS,isomer #1	CN(C(=O)C1=CC(OC2=CC=C(N(C(=O)N(C3=CC=C(Cl)C(C(F)(F)F)=C3)[Si](C)(C)C(C)(C)C)[Si](C)(C)C(C)(C)C)C=C2)=CC=N1)[Si](C)(C)C(C)(C)C	3888.5	Standard polar	33892256

Spectra

GC-MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted GC-MS	Predicted GC-MS Spectrum - Sorafenib GC-MS (Non-derivatized) - 70eV, Positive	splash10-022j-2972400000-d028d5e696594206a526	2017-09-01	Wishart Lab	View Spectrum
Predicted GC-MS	Predicted GC-MS Spectrum - Sorafenib GC-MS (Non-derivatized) - 70eV, Positive	Not Available	2021-10-12	Wishart Lab	View Spectrum

MS/MS Spectra

Spectrum Type	Description	Splash Key	Deposition Date	Source	View
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 10V, Positive-QTOF	splash10-014i-0130900000-b23ba9e8bd12e0916813	2016-08-01	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 20V, Positive-QTOF	splash10-00rg-0490300000-db91bca5efaa6389647b	2016-08-01	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 40V, Positive-QTOF	splash10-0a4r-3950000000-ae1180c0143c97f5e1f8	2016-08-01	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 10V, Negative-QTOF	splash10-01ox-0550900000-6151f8a0f4158ca5b6af	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 20V, Negative-QTOF	splash10-0006-0890300000-869fd311854027fc3dae	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 40V, Negative-QTOF	splash10-0006-3910000000-ad78334ecc783ea7c79a	2016-08-03	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 10V, Positive-QTOF	splash10-014i-0000900000-b1201d450369389781af	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 20V, Positive-QTOF	splash10-01b9-0050900000-638480ee259c1d75f5a2	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 40V, Positive-QTOF	splash10-00dr-0592200000-cc7aee9246b29d89cb4e	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 10V, Negative-QTOF	splash10-0006-0900000000-d85fcc5d4d516b9d75fd	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 20V, Negative-QTOF	splash10-0006-0900000000-59cfe242fba11ec110aa	2021-09-24	Wishart Lab	View Spectrum
Predicted LC-MS/MS	Predicted LC-MS/MS Spectrum - Sorafenib 40V, Negative-QTOF	splash10-0006-1900000000-ffd2c146e4b4655d855d	2021-09-24	Wishart Lab	View Spectrum

Biological Properties

Cellular Locations

Cytoplasm
Membrane

Biospecimen Locations

Blood
Urine

Tissue Locations

Not Available

Pathways

Name	SMPDB/PathBank	KEGG
Sorafenib Metabolism Pathway		Not Available

Normal Concentrations

Biospecimen	Status	Value	Age	Sex	Condition	Reference	Details
Blood	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry DB00398	21059682	details
Urine	Expected but not Quantified	Not Quantified	Not Available	Not Available	Taking drug identified by DrugBank entry DB00398	21059682	details

Abnormal Concentrations

Not Available

Predicted Concentrations

Biospecimen	Value	Original age	Original sex	Original condition	Comments
Blood	0.000 uM	Adult (>18 years old)	Both	Normal	Predicted based on drug qualities
Blood	0.000 umol/mmol creatinine	Adult (>18 years old)	Both	Normal	Predicted based on drug qualities

Associated Disorders and Diseases

Disease References

None

Associated OMIM IDs

None

External Links

DrugBank ID

DB00398

Phenol Explorer Compound ID

Not Available

FooDB ID

Not Available

KNApSAcK ID

Not Available

Chemspider ID

187440

KEGG Compound ID

Not Available

BioCyc ID

Not Available

BiGG ID

Not Available

Wikipedia Link

Sorafenib

METLIN ID

Not Available

PubChem Compound

216239

PDB ID

Not Available

ChEBI ID

50924

Food Biomarker Ontology

Not Available

VMH ID

Not Available

MarkerDB ID

Not Available

Good Scents ID

Not Available

References

Synthesis Reference

Not Available

Material Safety Data Sheet (MSDS)

Not Available

General References

(). FDA label . .

Only showing the first 10 proteins. There are 21 proteins in total.

Show all enzymes and transporters

Enzymes

Enzyme Details

1. UDP-glucuronosyltransferase 1-9

General function:: Involved in transferase activity, transferring hexosyl groups
Specific function:: UDPGT is of major importance in the conjugation and subsequent elimination of potentially toxic xenobiotics and endogenous compounds. This isoform has specificity for phenols.
Gene Name:: UGT1A9
Uniprot ID:: O60656
Molecular weight:: 59940.495

References

Gomo C, Coriat R, Faivre L, Mir O, Ropert S, Billemont B, Dauphin A, Tod M, Goldwasser F, Blanchet B: Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4. doi: 10.1007/s10637-010-9514-3. Epub 2010 Aug 13. [PubMed:20706860 ]
van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
Keating GM, Santoro A: Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs. 2009;69(2):223-40. doi: 10.2165/00003495-200969020-00006. [PubMed:19228077 ]

Enzyme Details

2. Cytochrome P450 3A4

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation reactions (e.g. caffeine 8-oxidation, omeprazole sulphoxidation, midazolam 1'-hydroxylation and midazolam 4-hydroxylation) of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. Acts as a 1,8-cineole 2-exo-monooxygenase. The enzyme also hydroxylates etoposide.
Gene Name:: CYP3A4
Uniprot ID:: P08684
Molecular weight:: 57255.585

References

Gomo C, Coriat R, Faivre L, Mir O, Ropert S, Billemont B, Dauphin A, Tod M, Goldwasser F, Blanchet B: Pharmacokinetic interaction involving sorafenib and the calcium-channel blocker felodipine in a patient with hepatocellular carcinoma. Invest New Drugs. 2011 Dec;29(6):1511-4. doi: 10.1007/s10637-010-9514-3. Epub 2010 Aug 13. [PubMed:20706860 ]
van Erp NP, Gelderblom H, Guchelaar HJ: Clinical pharmacokinetics of tyrosine kinase inhibitors. Cancer Treat Rev. 2009 Dec;35(8):692-706. doi: 10.1016/j.ctrv.2009.08.004. Epub 2009 Sep 5. [PubMed:19733976 ]
Flaherty KT, Lathia C, Frye RF, Schuchter L, Redlinger M, Rosen M, O'Dwyer PJ: Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8. doi: 10.1007/s00280-011-1585-0. Epub 2011 Feb 25. [PubMed:21350850 ]

Enzyme Details

3. Cytochrome P450 2C9

General function:: Involved in monooxygenase activity
Specific function:: Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It oxidizes a variety of structurally unrelated compounds, including steroids, fatty acids, and xenobiotics. This enzyme contributes to the wide pharmacokinetics variability of the metabolism of drugs such as S-warfarin, diclofenac, phenytoin, tolbutamide and losartan.
Gene Name:: CYP2C9
Uniprot ID:: P11712
Molecular weight:: 55627.365

References

Flaherty KT, Lathia C, Frye RF, Schuchter L, Redlinger M, Rosen M, O'Dwyer PJ: Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8. doi: 10.1007/s00280-011-1585-0. Epub 2011 Feb 25. [PubMed:21350850 ]

Enzyme Details

4. Cytochrome P450 2C19

General function:: Involved in monooxygenase activity
Specific function:: Responsible for the metabolism of a number of therapeutic agents such as the anticonvulsant drug S-mephenytoin, omeprazole, proguanil, certain barbiturates, diazepam, propranolol, citalopram and imipramine.
Gene Name:: CYP2C19
Uniprot ID:: P33261
Molecular weight:: 55944.565

References

Flaherty KT, Lathia C, Frye RF, Schuchter L, Redlinger M, Rosen M, O'Dwyer PJ: Interaction of sorafenib and cytochrome P450 isoenzymes in patients with advanced melanoma: a phase I/II pharmacokinetic interaction study. Cancer Chemother Pharmacol. 2011 Nov;68(5):1111-8. doi: 10.1007/s00280-011-1585-0. Epub 2011 Feb 25. [PubMed:21350850 ]

Enzyme Details

5. RAF proto-oncogene serine/threonine-protein kinase

General function:: Involved in intracellular signaling pathway
Specific function:: Involved in the transduction of mitogenic signals from the cell membrane to the nucleus. Part of the Ras-dependent signaling pathway from receptors to the nucleus. Protects cells from apoptosis mediated by STK3
Gene Name:: RAF1
Uniprot ID:: P04049
Molecular weight:: 73051.0

References

Adnane L, Trail PA, Taylor I, Wilhelm SM: Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol. 2006;407:597-612. [PubMed:16757355 ]
Gollob JA, Wilhelm S, Carter C, Kelley SL: Role of Raf kinase in cancer: therapeutic potential of targeting the Raf/MEK/ERK signal transduction pathway. Semin Oncol. 2006 Aug;33(4):392-406. [PubMed:16890795 ]
Huether A, Hopfner M, Baradari V, Schuppan D, Scherubl H: Sorafenib alone or as combination therapy for growth control of cholangiocarcinoma. Biochem Pharmacol. 2007 May 1;73(9):1308-17. Epub 2007 Jan 5. [PubMed:17266941 ]
Cascone T, Gridelli C, Ciardiello F: Combined targeted therapies in non-small cell lung cancer: a winner strategy? Curr Opin Oncol. 2007 Mar;19(2):98-102. [PubMed:17272980 ]
Gridelli C, Maione P, Del Gaizo F, Colantuoni G, Guerriero C, Ferrara C, Nicolella D, Comunale D, De Vita A, Rossi A: Sorafenib and sunitinib in the treatment of advanced non-small cell lung cancer. Oncologist. 2007 Feb;12(2):191-200. [PubMed:17296815 ]
Lu X, Tang X, Guo W, Ren T, Zhao H: Sorafenib induces growth inhibition and apoptosis of human chondrosarcoma cells by blocking the RAF/ERK/MEK pathway. J Surg Oncol. 2010 Dec 1;102(7):821-6. doi: 10.1002/jso.21661. [PubMed:20812347 ]

Enzyme Details

6. Vascular endothelial growth factor receptor 3

General function:: Involved in protein kinase activity
Specific function:: Receptor for VEGFC. Has a tyrosine-protein kinase activity
Gene Name:: FLT4
Uniprot ID:: P35916
Molecular weight:: 145597.3

References

Lathia C, Lettieri J, Cihon F, Gallentine M, Radtke M, Sundaresan P: Lack of effect of ketoconazole-mediated CYP3A inhibition on sorafenib clinical pharmacokinetics. Cancer Chemother Pharmacol. 2006 May;57(5):685-92. Epub 2005 Aug 25. [PubMed:16133532 ]
Adnane L, Trail PA, Taylor I, Wilhelm SM: Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol. 2006;407:597-612. [PubMed:16757355 ]
Gridelli C, Maione P, Del Gaizo F, Colantuoni G, Guerriero C, Ferrara C, Nicolella D, Comunale D, De Vita A, Rossi A: Sorafenib and sunitinib in the treatment of advanced non-small cell lung cancer. Oncologist. 2007 Feb;12(2):191-200. [PubMed:17296815 ]
Strumberg D: Preclinical and clinical development of the oral multikinase inhibitor sorafenib in cancer treatment. Drugs Today (Barc). 2005 Dec;41(12):773-84. [PubMed:16474853 ]
Reddy GK, Bukowski RM: Sorafenib: recent update on activity as a single agent and in combination with interferon-alpha2 in patients with advanced-stage renal cell carcinoma. Clin Genitourin Cancer. 2006 Mar;4(4):246-8. [PubMed:16729906 ]

Enzyme Details

7. FL cytokine receptor

General function:: Involved in protein kinase activity
Specific function:: Receptor for the FL cytokine. Has a tyrosine-protein kinase activity
Gene Name:: FLT3
Uniprot ID:: P36888
Molecular weight:: 112902.5

References

Auclair D, Miller D, Yatsula V, Pickett W, Carter C, Chang Y, Zhang X, Wilkie D, Burd A, Shi H, Rocks S, Gedrich R, Abriola L, Vasavada H, Lynch M, Dumas J, Trail PA, Wilhelm SM: Antitumor activity of sorafenib in FLT3-driven leukemic cells. Leukemia. 2007 Mar;21(3):439-45. Epub 2007 Jan 4. [PubMed:17205056 ]
Lierman E, Lahortiga I, Van Miegroet H, Mentens N, Marynen P, Cools J: The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and overcome resistance to other small molecule inhibitors. Haematologica. 2007 Jan;92(1):27-34. [PubMed:17229632 ]

Enzyme Details

8. Vascular endothelial growth factor receptor 2

General function:: Involved in protein kinase activity
Specific function:: Receptor for VEGF or VEGFC. Has a tyrosine-protein kinase activity. The VEGF-kinase ligand/receptor signaling system plays a key role in vascular development and regulation of vascular permeability. In case of HIV-1 infection, the interaction with extracellular viral Tat protein seems to enhance angiogenesis in Kaposi's sarcoma lesions
Gene Name:: KDR
Uniprot ID:: P35968
Molecular weight:: 151525.6

References

Schoffski P, Dumez H, Clement P, Hoeben A, Prenen H, Wolter P, Joniau S, Roskams T, Van Poppel H: Emerging role of tyrosine kinase inhibitors in the treatment of advanced renal cell cancer: a review. Ann Oncol. 2006 Aug;17(8):1185-96. Epub 2006 Jan 17. [PubMed:16418310 ]
Veronese ML, Mosenkis A, Flaherty KT, Gallagher M, Stevenson JP, Townsend RR, O'Dwyer PJ: Mechanisms of hypertension associated with BAY 43-9006. J Clin Oncol. 2006 Mar 20;24(9):1363-9. Epub 2006 Jan 30. [PubMed:16446323 ]
Rini BI: Sorafenib. Expert Opin Pharmacother. 2006 Mar;7(4):453-61. [PubMed:16503817 ]
Adnane L, Trail PA, Taylor I, Wilhelm SM: Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature. Methods Enzymol. 2006;407:597-612. [PubMed:16757355 ]
Lacouture ME, Desai A, Soltani K, Petronic-Rosic V, Laumann AE, Ratain MJ, Stadler WM: Inflammation of actinic keratoses subsequent to therapy with sorafenib, a multitargeted tyrosine-kinase inhibitor. Clin Exp Dermatol. 2006 Nov;31(6):783-5. Epub 2006 Jul 4. [PubMed:16824050 ]

Enzyme Details

9. Beta-type platelet-derived growth factor receptor

General function:: Involved in protein kinase activity
Specific function:: Receptor that binds specifically to PDGFB and PDGFD and has a tyrosine-protein kinase activity. Phosphorylates Tyr residues at the C-terminus of PTPN11 creating a binding site for the SH2 domain of GRB2
Gene Name:: PDGFRB
Uniprot ID:: P09619
Molecular weight:: 123966.9

References

Gollob JA: Sorafenib: scientific rationales for single-agent and combination therapy in clear-cell renal cell carcinoma. Clin Genitourin Cancer. 2005 Dec;4(3):167-74. [PubMed:16425993 ]
Guida T, Anaganti S, Provitera L, Gedrich R, Sullivan E, Wilhelm SM, Santoro M, Carlomagno F: Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res. 2007 Jun 1;13(11):3363-9. [PubMed:17545544 ]
Unnithan J, Rini BI: The role of targeted therapy in metastatic renal cell carcinoma. ScientificWorldJournal. 2007 Mar 2;7:800-7. [PubMed:17619763 ]

Enzyme Details

10. Mast/stem cell growth factor receptor

General function:: Involved in protein kinase activity
Specific function:: This is the receptor for stem cell factor (mast cell growth factor). It has a tyrosine-protein kinase activity. Binding of the ligands leads to the autophosphorylation of KIT and its association with substrates such as phosphatidylinositol 3-kinase (Pi3K)
Gene Name:: KIT
Uniprot ID:: P10721
Molecular weight:: 109863.7

References

Guida T, Anaganti S, Provitera L, Gedrich R, Sullivan E, Wilhelm SM, Santoro M, Carlomagno F: Sorafenib inhibits imatinib-resistant KIT and platelet-derived growth factor receptor beta gatekeeper mutants. Clin Cancer Res. 2007 Jun 1;13(11):3363-9. [PubMed:17545544 ]
Koch CA, Gimm O, Vortmeyer AO, Al-Ali HK, Lamesch P, Ott R, Kluge R, Bierbach U, Tannapfel A: Does the expression of c-kit (CD117) in neuroendocrine tumors represent a target for therapy? Ann N Y Acad Sci. 2006 Aug;1073:517-26. [PubMed:17102120 ]
Lierman E, Lahortiga I, Van Miegroet H, Mentens N, Marynen P, Cools J: The ability of sorafenib to inhibit oncogenic PDGFRbeta and FLT3 mutants and overcome resistance to other small molecule inhibitors. Haematologica. 2007 Jan;92(1):27-34. [PubMed:17229632 ]
Cascone T, Gridelli C, Ciardiello F: Combined targeted therapies in non-small cell lung cancer: a winner strategy? Curr Opin Oncol. 2007 Mar;19(2):98-102. [PubMed:17272980 ]
Liu L, Cao Y, Chen C, Zhang X, McNabola A, Wilkie D, Wilhelm S, Lynch M, Carter C: Sorafenib blocks the RAF/MEK/ERK pathway, inhibits tumor angiogenesis, and induces tumor cell apoptosis in hepatocellular carcinoma model PLC/PRF/5. Cancer Res. 2006 Dec 15;66(24):11851-8. [PubMed:17178882 ]

Transporters

Enzyme Details

1. Canalicular multispecific organic anion transporter 1

General function:: Involved in ATP binding
Specific function:: Mediates hepatobiliary excretion of numerous organic anions. May function as a cellular cisplatin transporter
Gene Name:: ABCC2
Uniprot ID:: Q92887
Molecular weight:: 174205.6

References

Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380 ]

Enzyme Details

2. Multidrug resistance protein 1

General function:: Involved in ATP binding
Specific function:: Energy-dependent efflux pump responsible for decreased drug accumulation in multidrug-resistant cells
Gene Name:: ABCB1
Uniprot ID:: P08183
Molecular weight:: 141477.3

References

Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380 ]
Lagas JS, van Waterschoot RA, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH: Breast cancer resistance protein and P-glycoprotein limit sorafenib brain accumulation. Mol Cancer Ther. 2010 Feb;9(2):319-26. doi: 10.1158/1535-7163.MCT-09-0663. Epub 2010 Jan 26. [PubMed:20103600 ]

Enzyme Details

3. ATP-binding cassette sub-family G member 2

General function:: Involved in ATP binding
Specific function:: Xenobiotic transporter that may play an important role in the exclusion of xenobiotics from the brain. May be involved in brain-to-blood efflux. Appears to play a major role in the multidrug resistance phenotype of several cancer cell lines. When overexpressed, the transfected cells become resistant to mitoxantrone, daunorubicin and doxorubicin, display diminished intracellular accumulation of daunorubicin, and manifest an ATP- dependent increase in the efflux of rhodamine 123
Gene Name:: ABCG2
Uniprot ID:: Q9UNQ0
Molecular weight:: 72313.5

References

Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380 ]
Lagas JS, van Waterschoot RA, Sparidans RW, Wagenaar E, Beijnen JH, Schinkel AH: Breast cancer resistance protein and P-glycoprotein limit sorafenib brain accumulation. Mol Cancer Ther. 2010 Feb;9(2):319-26. doi: 10.1158/1535-7163.MCT-09-0663. Epub 2010 Jan 26. [PubMed:20103600 ]

Enzyme Details

4. Multidrug resistance-associated protein 4

General function:: Involved in ATP binding
Specific function:: May be an organic anion pump relevant to cellular detoxification
Gene Name:: ABCC4
Uniprot ID:: O15439
Molecular weight:: 149525.3

References

Hu S, Chen Z, Franke R, Orwick S, Zhao M, Rudek MA, Sparreboom A, Baker SD: Interaction of the multikinase inhibitors sorafenib and sunitinib with solute carriers and ATP-binding cassette transporters. Clin Cancer Res. 2009 Oct 1;15(19):6062-9. doi: 10.1158/1078-0432.CCR-09-0048. Epub 2009 Sep 22. [PubMed:19773380 ]

Only showing the first 10 proteins. There are 21 proteins in total.

Show all enzymes and transporters

Showing metabocard for Sorafenib (HMDB0014542)

MOL for HMDB0014542 (Sorafenib)

3D MOL for HMDB0014542 (Sorafenib)

3D SDF for HMDB0014542 (Sorafenib)

3D-SDF for HMDB0014542 (Sorafenib)

PDB for HMDB0014542 (Sorafenib)

3D PDB for HMDB0014542 (Sorafenib)

SMILES for HMDB0014542 (Sorafenib)

INCHI for HMDB0014542 (Sorafenib)

Structure for HMDB0014542 (Sorafenib)

3D Structure for HMDB0014542 (Sorafenib)

Predicted Collision Cross Sections

Predicted Retention Times

Underivatized

Predicted Kovats Retention Indices

Underivatized

Derivatized

GC-MS Spectra

MS/MS Spectra

Enzymes

References

References

References

References

References

References

References

References

References

References

Transporters

References

References

References

References