Details of the Drug

General Information of Drug (ID: DMF98Q0)

Drug Name
Momelotinib
Synonyms
Cyt387; 1056634-68-4; MOMELOTINIB; Cyt-387; N-(Cyanomethyl)-4-(2-((4-morpholinophenyl)amino)pyrimidin-4-yl)benzamide; CYT 387; CYT 11387; UNII-6O01GMS00P; N-(cyanomethyl)-4-(2-(4-morpholinophenylamino)pyrimidin-4-yl)benzamide; 6O01GMS00P; CHEMBL1078178; AK102858; N-(cyanomethyl)-4-(2-((4-(4-morpholinyl)phenyl)amino)-4-pyrimidinyl)benzamide; N-(cyanomethyl)-4-(2-{[4-(morpholin-4-yl)phenyl]amino}pyrimidin-4-yl)benzamide; CYT387 sulfate salt; N-(Cyanomethyl)-4-(2-((4-morpholinophenyl)-amino)pyrimidin-4-yl)benzamide
Indication
Disease Entry ICD 11 Status REF
Myelofibrosis 2A20.2 Approved [1]
Polycythemia vera 2A20.4 Phase 2 [2]
Thrombocythemia 3B63 Phase 2 [2]
Drug Type
Small molecular drug
Structure
3D MOL 2D MOL
#Ro5 Violations (Lipinski): 0 Molecular Weight (mw) 414.5
Logarithm of the Partition Coefficient (xlogp) 2.6
Rotatable Bond Count (rotbonds) 6
Hydrogen Bond Donor Count (hbonddonor) 2
Hydrogen Bond Acceptor Count (hbondacc) 7
Chemical Identifiers
Formula
C23H22N6O2
IUPAC Name
N-(cyanomethyl)-4-[2-(4-morpholin-4-ylanilino)pyrimidin-4-yl]benzamide
Canonical SMILES
C1COCCN1C2=CC=C(C=C2)NC3=NC=CC(=N3)C4=CC=C(C=C4)C(=O)NCC#N
InChI
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)
InChIKey
ZVHNDZWQTBEVRY-UHFFFAOYSA-N
Cross-matching ID
PubChem CID
25062766
ChEBI ID
CHEBI:91407
CAS Number
1056634-68-4
DrugBank ID
DB11763
TTD ID
D0D5ZJ
INTEDE ID
DR1880
Combinatorial Drugs (CBD) Click to Jump to the Detailed CBD Information of This Drug
Repurposed Drugs (RPD) Click to Jump to the Detailed RPD Information of This Drug

Molecular Interaction Atlas of This Drug


Drug Therapeutic Target (DTT)
DTT Name DTT ID UniProt ID MOA REF
Janus kinase 1 (JAK-1) TT6DM01 JAK1_HUMAN Modulator [1]
Janus kinase 2 (JAK-2) TTRMX3V JAK2_HUMAN Modulator [3]

Drug-Metabolizing Enzyme (DME)
DME Name DME ID UniProt ID MOA REF
Cytochrome P450 3A4 (CYP3A4) DE4LYSA CP3A4_HUMAN Substrate [4]
Cytochrome P450 2C9 (CYP2C9) DE5IED8 CP2C9_HUMAN Substrate [4]
Mephenytoin 4-hydroxylase (CYP2C19) DEGTFWK CP2CJ_HUMAN Substrate [4]
Cytochrome P450 1A2 (CYP1A2) DEJGDUW CP1A2_HUMAN Substrate [4]
Cytochrome P450 2C8 (CYP2C8) DES5XRU CP2C8_HUMAN Substrate [4]

Drug Off-Target (DOT)
DOT Name DOT ID UniProt ID Interaction REF
Apoptosis regulator BAX (BAX) OTAW0V4V BAX_HUMAN Gene/Protein Processing [5]
Apoptosis regulator Bcl-2 (BCL2) OT9DVHC0 BCL2_HUMAN Gene/Protein Processing [5]
Apoptotic protease-activating factor 1 (APAF1) OTJWIVY0 APAF_HUMAN Gene/Protein Processing [5]
Bcl2-associated agonist of cell death (BAD) OT63ERYM BAD_HUMAN Gene/Protein Processing [5]
Caspase-3 (CASP3) OTIJRBE7 CASP3_HUMAN Protein Interaction/Cellular Processes [5]
Eukaryotic translation initiation factor 4E (EIF4E) OTDAWNLA IF4E_HUMAN Gene/Protein Processing [5]
Eukaryotic translation initiation factor 4E-binding protein 3 (EIF4EBP3) OTYY2WS5 4EBP3_HUMAN Gene/Protein Processing [5]
G1/S-specific cyclin-D1 (CCND1) OT8HPTKJ CCND1_HUMAN Gene/Protein Processing [5]
RAC-alpha serine/threonine-protein kinase (AKT1) OT8H2YY7 AKT1_HUMAN Post-Translational Modifications [5]
Ribosomal protein S6 kinase beta-1 (RPS6KB1) OTAELNGX KS6B1_HUMAN Gene/Protein Processing [5]
Molecular Interaction Atlas (MIA) Jump to Detail Molecular Interaction Atlas of This Drug

Molecular Expression Atlas of This Drug

The Studied Disease Myelofibrosis
ICD Disease Classification 2A20.2
Molecule Name Molecule Type Gene Name p-value Fold-Change Z-score
Janus kinase 2 (JAK-2) DTT JAK2 2.46E-01 -0.41 -0.6
Cytochrome P450 2C8 (CYP2C8) DME CYP2C8 6.03E-01 7.61E-02 6.10E-01
Cytochrome P450 1A2 (CYP1A2) DME CYP1A2 1.93E-01 3.11E-01 8.10E-01
Mephenytoin 4-hydroxylase (CYP2C19) DME CYP2C19 1.67E-02 8.33E-01 1.75E+00
Cytochrome P450 2C9 (CYP2C9) DME CYP2C9 1.21E-01 5.16E-01 1.33E+00
Cytochrome P450 3A4 (CYP3A4) DME CYP3A4 1.23E-01 4.92E-01 1.13E+00
Molecular Expression Atlas (MEA) Jump to Detail Molecular Expression Atlas of This Drug

References

1 FDA Approved Drug Products from FDA Official Website. 2023. Application Number: 216873
2 Clinical pipeline report, company report or official report of the Pharmaceutical Research and Manufacturers of America (PhRMA)
3 Genetic determinants of response and survival in momelotinib-treated patients with myelofibrosis.Leukemia.2015 Mar;29(3):741-4.
4 Pharmacokinetics and disposition of momelotinib revealed a disproportionate human metabolite-resolution for clinical development. Drug Metab Dispos. 2018 Mar;46(3):237-247.
5 The effect of quercetin nanoparticle on cervical cancer progression by inducing apoptosis, autophagy and anti-proliferation via JAK2 suppression. Biomed Pharmacother. 2016 Aug;82:595-605. doi: 10.1016/j.biopha.2016.05.029. Epub 2016 Jun 9.