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Details

Stereochemistry ACHIRAL
Molecular Formula C23H22N6O2
Molecular Weight 414.4598
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MOMELOTINIB

SMILES

O=C(NCC#N)C1=CC=C(C=C1)C2=NC(NC3=CC=C(C=C3)N4CCOCC4)=NC=C2

InChI

InChIKey=ZVHNDZWQTBEVRY-UHFFFAOYSA-N
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)

HIDE SMILES / InChI

Molecular Formula C23H22N6O2
Molecular Weight 414.4598
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment: Description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/19295546 | https://www.ncbi.nlm.nih.gov/pubmed/23459451

Momelotinib (CYT387) is an ATP-competitive small molecule that potently inhibits JAK1/JAK2 kinases. Momelotinib is developing by Gilead Sciences for the oral treatment of pancreatic and non-small cell lung cancers, and myeloproliferative disorders (including myelofibrosis, essential thrombocythaemia and polycythaemia vera).

CNS Activity

Curator's Comment: Momelotinib (CYT387) is brain penetrant in mice. No human data available.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
11.0 nM [IC50]
18.0 nM [IC50]
Conditions
Overview

Overview

CYP3A4CYP2C9CYP2D6hERG


OverviewOther

Other InhibitorOther SubstrateOther Inducer







Drug as perpetrator​

Drug as perpetrator​

TargetModalityActivityMetaboliteClinical evidence
yes [IC50 5.8048 uM]
Drug as victim
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs).
2009 Oct 15
CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms.
2010 Jun 24
P-glycoprotein (MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) restrict brain accumulation of the JAK1/2 inhibitor, CYT387.
2013 Oct
Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden.
2014 May 6
Momelotinib in myelofibrosis: JAK1/2 inhibitor with a role in treating and understanding the anemia.
2017 Feb
Patents

Sample Use Guides

150-300 mg/day. Maximum tolerated dose of momelotinib was found to be 300 mg/day in the phase I portion of a phase I/II study (NCT00935987) in patients with myelofibrosis. At the higher dose level of 400 mg/day, two of six patients experienced dose-limiting toxicities.
Route of Administration: Oral
0.5 and 1.5 uM CYT387 caused growth suppression and apoptosis in JAK2-dependent hematopoietic cell lines, while nonhematopoietic cell lines were unaffected.
Substance Class Chemical
Created
by admin
on Sat Dec 16 17:21:43 UTC 2023
Edited
by admin
on Sat Dec 16 17:21:43 UTC 2023
Record UNII
6O01GMS00P
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
MOMELOTINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
MOMELOTINIB [USAN]
Common Name English
Momelotinib [WHO-DD]
Common Name English
CYT387
Code English
CYT-0387
Code English
CYT-387
Code English
CYT-11387
Common Name English
momelotinib [INN]
Common Name English
N-(CYANOMETHYL)-4-(2-(4-MORPHOLINOANILINO)PYRIMIDIN-4-YL)BENZAMIDE
Systematic Name English
GS-0387
Code English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
NCI_THESAURUS C129825
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
FDA ORPHAN DRUG 311610
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
Code System Code Type Description
DRUG BANK
DB11763
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
NCI_THESAURUS
C88311
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
USAN
XX-160
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
INN
9480
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
FDA UNII
6O01GMS00P
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
EPA CompTox
DTXSID801026049
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
SMS_ID
100000163080
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
PUBCHEM
25062766
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
WIKIPEDIA
CYT387
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
ChEMBL
CHEMBL1078178
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
CHEBI
91407
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
CAS
1056634-68-4
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
EVMPD
SUB177206
Created by admin on Sat Dec 16 17:21:48 UTC 2023 , Edited by admin on Sat Dec 16 17:21:48 UTC 2023
PRIMARY
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TARGET -> INHIBITOR
SALT/SOLVATE -> PARENT
METABOLIC ENZYME -> SUBSTRATE
MINOR
METABOLIC ENZYME -> SUBSTRATE
METABOLIC ENZYME -> SUBSTRATE
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METABOLIC ENZYME -> SUBSTRATE
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MAJOR
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METABOLITE -> PARENT
METABOLITE -> PARENT
MAJOR
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METABOLITE ACTIVE -> PARENT
MAJOR
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FECAL
METABOLITE -> PARENT
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ACTIVE MOIETY
Name Property Type Amount Referenced Substance Defining Parameters References
Tmax PHARMACOKINETIC
Biological Half-life PHARMACOKINETIC