Hmdb loader
You are using an unsupported browser. Please upgrade your browser to a newer version to get the best experience on Human Metabolome Database.
Record Information
Version5.0
StatusDetected but not Quantified
Creation Date2021-09-11 14:22:55 UTC
Update Date2021-09-26 23:09:19 UTC
HMDB IDHMDB0254901
Secondary Accession NumbersNone
Metabolite Identification
Common NameMotesanib
DescriptionMotesanib, also known as AMG 706, belongs to the class of organic compounds known as indolines. Indolines are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole. It is an orally administered small molecule belonging to angiokinase inhibitor class which acts as an antagonist of VEGF receptors, platelet-derived growth factor receptors, and stem cell factor receptors. Motesanib is a very strong basic compound (based on its pKa). However a later and more detailed Phase III trial failed to show any benefit for the treatment of NSCLC. After clinical trials in thyroid cancer, non-small cell lung cancer, gastrointestinal stromal cancer, colorectal cancer, and breast cancer, the drug was not found to show sufficient efficacy for further development, and development was abandoned by Takeda. Two phase II clinical trials for thyroid cancer showed promising results. Motesanib was originally investigated for effectiveness against advanced nonsquamous non-small-cell lung cancer (NSCLC), with Phase II trials indicating an effectiveness comparable to bevacizumab when they were both used in combination with paclitaxel/carboplatin. Phase II testing against persistent or recurrent ovarian, fallopian tube and primary peritoneal carcinomas was also unsuccessful. A second Phase III trial was started in 2012, which focused on patients from Asian backgrounds (performed on the bases of subgroup analysis) however this also failed to meet its primary endpoint. The drug has undergone a Phase II evaluation as first-line therapy for breast cancer however this study found no evidence to support further investigation. This compound has been identified in human blood as reported by (PMID: 31557052 ). Motesanib is not a naturally occurring metabolite and is only found in those individuals exposed to this compound or its derivatives. Technically Motesanib is part of the human exposome. The exposome can be defined as the collection of all the exposures of an individual in a lifetime and how those exposures relate to health. An individual's exposure begins before birth and includes insults from environmental and occupational sources.
Structure
Thumb
Synonyms
ValueSource
N-(2,3-Dihydro-3,3-dimethyl-1H-indol-6-yl)-2-((4-pyridinylmethyl)amino)-3-pyridinecarboxamideChEBI
AMG 706Kegg
Motesanib diphosphateMeSH
AMG-706MeSH
ImetelstatMeSH
Chemical FormulaC22H23N5O
Average Molecular Weight373.4509
Monoisotopic Molecular Weight373.190260383
IUPAC NameN-(3,3-dimethyl-2,3-dihydro-1H-indol-6-yl)-2-[(pyridin-4-ylmethyl)amino]pyridine-3-carboximidic acid
Traditional Namemotesanib
CAS Registry NumberNot Available
SMILES
CC1(C)CNC2=C1C=CC(=C2)N=C(O)C1=C(NCC2=CC=NC=C2)N=CC=C1
InChI Identifier
InChI=1S/C22H23N5O/c1-22(2)14-26-19-12-16(5-6-18(19)22)27-21(28)17-4-3-9-24-20(17)25-13-15-7-10-23-11-8-15/h3-12,26H,13-14H2,1-2H3,(H,24,25)(H,27,28)
InChI KeyRAHBGWKEPAQNFF-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as indolines. Indolines are compounds containing an indole moiety, which consists of pyrrolidine ring fused to benzene to form 2,3-dihydroindole.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassIndoles and derivatives
Sub ClassIndolines
Direct ParentIndolines
Alternative Parents
Substituents
  • Dihydroindole
  • Nicotinamide
  • Pyridinecarboxamide
  • Pyridine carboxylic acid or derivatives
  • Aminopyridine
  • Secondary aliphatic/aromatic amine
  • Aralkylamine
  • Imidolactam
  • Benzenoid
  • Pyridine
  • Heteroaromatic compound
  • Vinylogous amide
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Amino acid or derivatives
  • Azacycle
  • Secondary amine
  • Carboxylic acid derivative
  • Organonitrogen compound
  • Organic oxygen compound
  • Organic nitrogen compound
  • Hydrocarbon derivative
  • Amine
  • Organooxygen compound
  • Organopnictogen compound
  • Organic oxide
  • Aromatic heteropolycyclic compound
Molecular FrameworkAromatic heteropolycyclic compounds
External Descriptors
Ontology
Physiological effectNot Available
Disposition
ProcessNot Available
RoleNot Available
Physical Properties
StateNot Available
Experimental Molecular Properties
PropertyValueReference
Melting PointNot AvailableNot Available
Boiling PointNot AvailableNot Available
Water SolubilityNot AvailableNot Available
LogPNot AvailableNot Available
Experimental Chromatographic PropertiesNot Available
Predicted Molecular Properties
PropertyValueSource
logP3.48ALOGPS
logP2.91ChemAxon
logS-4.6ALOGPS
pKa (Strongest Acidic)5.45ChemAxon
pKa (Strongest Basic)7.02ChemAxon
Physiological Charge1ChemAxon
Hydrogen Acceptor Count6ChemAxon
Hydrogen Donor Count3ChemAxon
Polar Surface Area82.43 ŲChemAxon
Rotatable Bond Count5ChemAxon
Refractivity115.53 m³·mol⁻¹ChemAxon
Polarizability41.44 ųChemAxon
Number of Rings4ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleNoChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+191.56230932474
DeepCCS[M-H]-189.20430932474
DeepCCS[M-2H]-223.3730932474
DeepCCS[M+Na]+198.59830932474
AllCCS[M+H]+193.532859911
AllCCS[M+H-H2O]+190.832859911
AllCCS[M+NH4]+196.132859911
AllCCS[M+Na]+196.832859911
AllCCS[M-H]-193.232859911
AllCCS[M+Na-2H]-193.032859911
AllCCS[M+HCOO]-192.932859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
MotesanibCC1(C)CNC2=C1C=CC(=C2)N=C(O)C1=C(NCC2=CC=NC=C2)N=CC=C14738.2Standard polar33892256
MotesanibCC1(C)CNC2=C1C=CC(=C2)N=C(O)C1=C(NCC2=CC=NC=C2)N=CC=C13588.1Standard non polar33892256
MotesanibCC1(C)CNC2=C1C=CC(=C2)N=C(O)C1=C(NCC2=CC=NC=C2)N=CC=C13451.7Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Motesanib,2TMS,isomer #1CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C213302.2Semi standard non polar33892256
Motesanib,2TMS,isomer #1CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C213115.6Standard non polar33892256
Motesanib,2TMS,isomer #1CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C214057.6Standard polar33892256
Motesanib,2TMS,isomer #2CC1(C)CNC2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C213251.0Semi standard non polar33892256
Motesanib,2TMS,isomer #2CC1(C)CNC2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C213071.0Standard non polar33892256
Motesanib,2TMS,isomer #2CC1(C)CNC2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C214156.7Standard polar33892256
Motesanib,2TMS,isomer #3CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C213171.3Semi standard non polar33892256
Motesanib,2TMS,isomer #3CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C213173.0Standard non polar33892256
Motesanib,2TMS,isomer #3CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C213890.1Standard polar33892256
Motesanib,3TMS,isomer #1CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C213183.5Semi standard non polar33892256
Motesanib,3TMS,isomer #1CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C213013.1Standard non polar33892256
Motesanib,3TMS,isomer #1CC1(C)CN([Si](C)(C)C)C2=CC(N=C(O[Si](C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C)=CC=C213806.6Standard polar33892256
Motesanib,2TBDMS,isomer #1CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C213665.7Semi standard non polar33892256
Motesanib,2TBDMS,isomer #1CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C213523.0Standard non polar33892256
Motesanib,2TBDMS,isomer #1CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3NCC3=CC=NC=C3)=CC=C214240.0Standard polar33892256
Motesanib,2TBDMS,isomer #2CC1(C)CNC2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C213595.2Semi standard non polar33892256
Motesanib,2TBDMS,isomer #2CC1(C)CNC2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C213499.4Standard non polar33892256
Motesanib,2TBDMS,isomer #2CC1(C)CNC2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C214300.2Standard polar33892256
Motesanib,2TBDMS,isomer #3CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C213531.5Semi standard non polar33892256
Motesanib,2TBDMS,isomer #3CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C213570.4Standard non polar33892256
Motesanib,2TBDMS,isomer #3CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C214091.0Standard polar33892256
Motesanib,3TBDMS,isomer #1CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C213654.5Semi standard non polar33892256
Motesanib,3TBDMS,isomer #1CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C213608.6Standard non polar33892256
Motesanib,3TBDMS,isomer #1CC1(C)CN([Si](C)(C)C(C)(C)C)C2=CC(N=C(O[Si](C)(C)C(C)(C)C)C3=CC=CN=C3N(CC3=CC=NC=C3)[Si](C)(C)C(C)(C)C)=CC=C214041.5Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Motesanib GC-MS (Non-derivatized) - 70eV, Positivesplash10-03di-2946000000-1ef0ca696060501f3f2a2021-09-24Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Motesanib GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Motesanib GC-MS (TMS_1_1) - 70eV, PositiveNot Available2021-11-04Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Motesanib GC-MS (TMS_1_2) - 70eV, PositiveNot Available2021-11-04Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Motesanib GC-MS (TMS_1_3) - 70eV, PositiveNot Available2021-11-04Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Motesanib GC-MS (TBDMS_1_1) - 70eV, PositiveNot Available2021-11-04Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Motesanib GC-MS (TBDMS_1_2) - 70eV, PositiveNot Available2021-11-04Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Motesanib GC-MS (TBDMS_1_3) - 70eV, PositiveNot Available2021-11-04Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 10V, Positive-QTOFsplash10-00di-0319000000-bbbc4c281a4482625f072017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 20V, Positive-QTOFsplash10-03di-0964000000-bba5a667744363751e612017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 40V, Positive-QTOFsplash10-001i-2910000000-f5a86b88d6e9b2275cf62017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 10V, Negative-QTOFsplash10-00di-0209000000-498dc66e76f2594d4be22017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 20V, Negative-QTOFsplash10-00ai-3928000000-a7604c4b45cc3a77a64d2017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 40V, Negative-QTOFsplash10-0036-9800000000-fd642651adf843ecf1a32017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 10V, Positive-QTOFsplash10-00dl-5009000000-dcd41693e3867ddd92ff2021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 20V, Positive-QTOFsplash10-0006-9001000000-798e475acde23e9e65862021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 40V, Positive-QTOFsplash10-0006-9110000000-125dab2f1311665d77c82021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 10V, Negative-QTOFsplash10-00di-0009000000-0c83a5fa76cb48159b4a2021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 20V, Negative-QTOFsplash10-00di-3229000000-ec7012978521c4c7e3522021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Motesanib 40V, Negative-QTOFsplash10-0a6r-5942000000-28ac66c588ffbe0d70f22021-10-12Wishart LabView Spectrum
Biological Properties
Cellular LocationsNot Available
Biospecimen Locations
  • Blood
Tissue LocationsNot Available
Pathways
Normal Concentrations
BiospecimenStatusValueAgeSexConditionReferenceDetails
BloodDetected but not QuantifiedNot QuantifiedNot SpecifiedNot SpecifiedNormal details
Abnormal Concentrations
Not Available
Associated Disorders and Diseases
Disease ReferencesNone
Associated OMIM IDsNone
DrugBank IDDB05575
Phenol Explorer Compound IDNot Available
FooDB IDNot Available
KNApSAcK IDNot Available
Chemspider IDNot Available
KEGG Compound IDNot Available
BioCyc IDNot Available
BiGG IDNot Available
Wikipedia LinkMotesanib
METLIN IDNot Available
PubChem Compound11667893
PDB IDNot Available
ChEBI ID51098
Food Biomarker OntologyNot Available
VMH IDNot Available
MarkerDB IDNot Available
Good Scents IDNot Available
References
Synthesis ReferenceNot Available
Material Safety Data Sheet (MSDS)Not Available
General References
  1. Barupal DK, Fiehn O: Generating the Blood Exposome Database Using a Comprehensive Text Mining and Database Fusion Approach. Environ Health Perspect. 2019 Sep;127(9):97008. doi: 10.1289/EHP4713. Epub 2019 Sep 26. [PubMed:31557052 ]