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Record Information
Version5.0
StatusDetected but not Quantified
Creation Date2021-09-11 07:49:13 UTC
Update Date2021-09-26 23:02:20 UTC
HMDB IDHMDB0250717
Secondary Accession NumbersNone
Metabolite Identification
Common NameMomelotinib
DescriptionMomelotinib, also known as CYT-387, belongs to the class of organic compounds known as phenylpyrimidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrimidine ring through a CC or CN bond. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions. Momelotinib is a moderately basic compound (based on its pKa). Additional potential treatment indications for momelotinib include other myeloproliferative neoplasms, cancer (solid and liquid tumors) and inflammatory conditions. As of 2011, momelotinib is being developed as a drug for myelofibrosis and currently undergoes Phase I/II clinical trials. Momelotinib (INN, formerly GS-0387, CYT-387) is an inhibitor of Janus kinases JAK1 and JAK2, acting as an ATP competitor with IC50 values of 11 and 18 nM, respectively. The drug was originally discovered by Australian drug discovery company Cytopia, then developed by YM BioSciences Inc (since acquired by Gilead Sciences as of 2013). The inhibitor is significantly less active towards other kinases, including JAK3 (IC50 0.16 μM). As of 2016, momelotinib is being investigated for primary myelofibrosis or post-polycythemia vera or post-essential thrombocythemia myelofibrosis (post-PV/ET MF), as well as a treatment for relapsed or refractory metastatic pancreatic ductal adenocarcinoma (in combination with capecitabine and oxaliplatin). This compound has been identified in human blood as reported by (PMID: 31557052 ). Momelotinib is not a naturally occurring metabolite and is only found in those individuals exposed to this compound or its derivatives. Technically Momelotinib 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-(Cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamideMeSH
CYT-387MeSH
CYT 387MeSH
CYT-11387cyt-387GS-0387momelotinibChEMBL
MomelotinibMeSH
Chemical FormulaC23H22N6O2
Average Molecular Weight414.469
Monoisotopic Molecular Weight414.180423972
IUPAC NameN-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide
Traditional NameN-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide
CAS Registry NumberNot Available
SMILES
O=C(NCC#N)C1=CC=C(C=C1)C1=CC=NC(NC2=CC=C(C=C2)N2CCOCC2)=N1
InChI Identifier
InChI=1S/C23H22N6O2/c24-10-12-25-22(30)18-3-1-17(2-4-18)21-9-11-26-23(28-21)27-19-5-7-20(8-6-19)29-13-15-31-16-14-29/h1-9,11H,12-16H2,(H,25,30)(H,26,27,28)
InChI KeyZVHNDZWQTBEVRY-UHFFFAOYSA-N
Chemical Taxonomy
Description Belongs to the class of organic compounds known as phenylpyrimidines. These are polycyclic aromatic compounds containing a benzene ring linked to a pyrimidine ring through a CC or CN bond. Pyrimidine is a 6-membered ring consisting of four carbon atoms and two nitrogen centers at the 1- and 3- ring positions.
KingdomOrganic compounds
Super ClassOrganoheterocyclic compounds
ClassDiazines
Sub ClassPyrimidines and pyrimidine derivatives
Direct ParentPhenylpyrimidines
Alternative Parents
Substituents
  • Phenylmorpholine
  • 4-phenylpyrimidine
  • 5-phenylpyrimidine
  • Benzamide
  • Benzoic acid or derivatives
  • Benzoyl
  • Tertiary aliphatic/aromatic amine
  • Dialkylarylamine
  • Aniline or substituted anilines
  • Aminopyrimidine
  • Benzenoid
  • Morpholine
  • Monocyclic benzene moiety
  • Oxazinane
  • Heteroaromatic compound
  • Tertiary amine
  • Amino acid or derivatives
  • Secondary carboxylic acid amide
  • Carboxamide group
  • Azacycle
  • Oxacycle
  • Nitrile
  • Carbonitrile
  • Secondary amine
  • Ether
  • Dialkyl ether
  • Carboxylic acid derivative
  • Hydrocarbon derivative
  • Organonitrogen compound
  • Amine
  • Organic oxygen compound
  • Organooxygen compound
  • Organic nitrogen compound
  • Organopnictogen compound
  • Organic oxide
  • Aromatic heteromonocyclic compound
Molecular FrameworkAromatic heteromonocyclic compounds
External DescriptorsNot Available
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
logP2.96ALOGPS
logP2.7ChemAxon
logS-4.1ALOGPS
pKa (Strongest Acidic)14.02ChemAxon
pKa (Strongest Basic)2.62ChemAxon
Physiological Charge0ChemAxon
Hydrogen Acceptor Count7ChemAxon
Hydrogen Donor Count2ChemAxon
Polar Surface Area103.17 ŲChemAxon
Rotatable Bond Count6ChemAxon
Refractivity118.46 m³·mol⁻¹ChemAxon
Polarizability44.23 ųChemAxon
Number of Rings4ChemAxon
BioavailabilityYesChemAxon
Rule of FiveYesChemAxon
Ghose FilterYesChemAxon
Veber's RuleNoChemAxon
MDDR-like RuleYesChemAxon
Predicted Chromatographic Properties

Predicted Collision Cross Sections

PredictorAdduct TypeCCS Value (Å2)Reference
DeepCCS[M+H]+195.97830932474
DeepCCS[M-H]-193.6230932474
DeepCCS[M-2H]-227.95230932474
DeepCCS[M+Na]+203.12730932474
AllCCS[M+H]+199.832859911
AllCCS[M+H-H2O]+197.432859911
AllCCS[M+NH4]+202.032859911
AllCCS[M+Na]+202.632859911
AllCCS[M-H]-197.832859911
AllCCS[M+Na-2H]-198.032859911
AllCCS[M+HCOO]-198.432859911

Predicted Kovats Retention Indices

Underivatized

MetaboliteSMILESKovats RI ValueColumn TypeReference
MomelotinibO=C(NCC#N)C1=CC=C(C=C1)C1=CC=NC(NC2=CC=C(C=C2)N2CCOCC2)=N14787.0Standard polar33892256
MomelotinibO=C(NCC#N)C1=CC=C(C=C1)C1=CC=NC(NC2=CC=C(C=C2)N2CCOCC2)=N14133.0Standard non polar33892256
MomelotinibO=C(NCC#N)C1=CC=C(C=C1)C1=CC=NC(NC2=CC=C(C=C2)N2CCOCC2)=N14652.9Semi standard non polar33892256

Derivatized

Derivative Name / StructureSMILESKovats RI ValueColumn TypeReference
Momelotinib,1TMS,isomer #1C[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(NC3=CC=C(N4CCOCC4)C=C3)=N2)C=C14314.7Semi standard non polar33892256
Momelotinib,1TMS,isomer #1C[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(NC3=CC=C(N4CCOCC4)C=C3)=N2)C=C14013.4Standard non polar33892256
Momelotinib,1TMS,isomer #1C[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(NC3=CC=C(N4CCOCC4)C=C3)=N2)C=C15732.6Standard polar33892256
Momelotinib,1TMS,isomer #2C[Si](C)(C)N(C1=CC=C(N2CCOCC2)C=C1)C1=NC=CC(C2=CC=C(C(=O)NCC#N)C=C2)=N14199.9Semi standard non polar33892256
Momelotinib,1TMS,isomer #2C[Si](C)(C)N(C1=CC=C(N2CCOCC2)C=C1)C1=NC=CC(C2=CC=C(C(=O)NCC#N)C=C2)=N13961.6Standard non polar33892256
Momelotinib,1TMS,isomer #2C[Si](C)(C)N(C1=CC=C(N2CCOCC2)C=C1)C1=NC=CC(C2=CC=C(C(=O)NCC#N)C=C2)=N15829.2Standard polar33892256
Momelotinib,2TMS,isomer #1C[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(N(C3=CC=C(N4CCOCC4)C=C3)[Si](C)(C)C)=N2)C=C14059.2Semi standard non polar33892256
Momelotinib,2TMS,isomer #1C[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(N(C3=CC=C(N4CCOCC4)C=C3)[Si](C)(C)C)=N2)C=C13920.1Standard non polar33892256
Momelotinib,2TMS,isomer #1C[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(N(C3=CC=C(N4CCOCC4)C=C3)[Si](C)(C)C)=N2)C=C15202.2Standard polar33892256
Momelotinib,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(NC3=CC=C(N4CCOCC4)C=C3)=N2)C=C14566.8Semi standard non polar33892256
Momelotinib,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(NC3=CC=C(N4CCOCC4)C=C3)=N2)C=C14250.6Standard non polar33892256
Momelotinib,1TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(NC3=CC=C(N4CCOCC4)C=C3)=N2)C=C15740.3Standard polar33892256
Momelotinib,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N(C1=CC=C(N2CCOCC2)C=C1)C1=NC=CC(C2=CC=C(C(=O)NCC#N)C=C2)=N14472.6Semi standard non polar33892256
Momelotinib,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N(C1=CC=C(N2CCOCC2)C=C1)C1=NC=CC(C2=CC=C(C(=O)NCC#N)C=C2)=N14164.9Standard non polar33892256
Momelotinib,1TBDMS,isomer #2CC(C)(C)[Si](C)(C)N(C1=CC=C(N2CCOCC2)C=C1)C1=NC=CC(C2=CC=C(C(=O)NCC#N)C=C2)=N15807.4Standard polar33892256
Momelotinib,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(N(C3=CC=C(N4CCOCC4)C=C3)[Si](C)(C)C(C)(C)C)=N2)C=C14511.7Semi standard non polar33892256
Momelotinib,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(N(C3=CC=C(N4CCOCC4)C=C3)[Si](C)(C)C(C)(C)C)=N2)C=C14360.3Standard non polar33892256
Momelotinib,2TBDMS,isomer #1CC(C)(C)[Si](C)(C)N(CC#N)C(=O)C1=CC=C(C2=CC=NC(N(C3=CC=C(N4CCOCC4)C=C3)[Si](C)(C)C(C)(C)C)=N2)C=C15176.9Standard polar33892256
Spectra

GC-MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted GC-MSPredicted GC-MS Spectrum - Momelotinib GC-MS (Non-derivatized) - 70eV, Positivesplash10-056r-1609000000-b3ce4ef5ff47b8064d1a2021-09-23Wishart LabView Spectrum
Predicted GC-MSPredicted GC-MS Spectrum - Momelotinib GC-MS (Non-derivatized) - 70eV, PositiveNot Available2021-10-12Wishart LabView Spectrum

MS/MS Spectra

Spectrum TypeDescriptionSplash KeyDeposition DateSourceView
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 10V, Positive-QTOFsplash10-066r-1118900000-8d9d0c12b438552e6f712017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 20V, Positive-QTOFsplash10-0a4i-1119100000-c3cb24bf07364e219e042017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 40V, Positive-QTOFsplash10-03di-1937000000-66f0da3b5a5cd5f5bb422017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 10V, Negative-QTOFsplash10-03di-1011900000-ce312b92228ee5f3abbe2017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 20V, Negative-QTOFsplash10-0il0-6577900000-c69ed3ca28c17c8fdf192017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 40V, Negative-QTOFsplash10-0a4l-9221000000-3505bb55281da145cc0c2017-07-26Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 10V, Positive-QTOFsplash10-014i-0002900000-34e5bd615815377813282021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 20V, Positive-QTOFsplash10-0a4i-0009000000-a363b581a4b01df0eec62021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 40V, Positive-QTOFsplash10-066r-0119000000-d17dc38a141319970da12021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 10V, Negative-QTOFsplash10-03di-0000900000-c1bcd1b72371ff37327a2021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 20V, Negative-QTOFsplash10-01q9-1009500000-819f434b2fd770b414a02021-10-12Wishart LabView Spectrum
Predicted LC-MS/MSPredicted LC-MS/MS Spectrum - Momelotinib 40V, Negative-QTOFsplash10-03di-0000900000-0645ab9815d7628fd8d32021-10-12Wishart 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 IDDB11763
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 LinkMomelotinib
METLIN IDNot Available
PubChem Compound25062766
PDB IDNot Available
ChEBI IDNot Available
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 ]