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Details

Stereochemistry ACHIRAL
Molecular Formula C23H22N6O2
Molecular Weight 414.4607
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of MOMELOTINIB

SMILES

c1cc(ccc1-c2ccnc(Nc3ccc(cc3)N4CCOCC4)n2)C(=O)NCC#N

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 414.4607
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
Curator's Comment:: 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

PubMed

PubMed

TitleDatePubMed
CYT387, a selective JAK1/JAK2 inhibitor: in vitro assessment of kinase selectivity and preclinical studies using cell lines and primary cells from polycythemia vera patients.
2009 Aug
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
The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells.
2011 Dec
Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis.
2013 Jun
P-glycoprotein (MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) restrict brain accumulation of the JAK1/2 inhibitor, CYT387.
2013 Oct
Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit.
2014 Apr
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 treatment-emergent neuropathy: prevalence, risk factors and outcome in 100 patients with myelofibrosis.
2015 Apr
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 Fri Jun 25 22:28:07 UTC 2021
Edited
by admin
on Fri Jun 25 22:28:07 UTC 2021
Record UNII
6O01GMS00P
Record Status Validated (UNII)
Record Version
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Name Type Language
MOMELOTINIB
INN   USAN   WHO-DD  
INN   USAN  
Official Name English
MOMELOTINIB [USAN]
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
MOMELOTINIB [WHO-DD]
Common Name English
GS-0387
Code English
Classification Tree Code System Code
NCI_THESAURUS C1967
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
NCI_THESAURUS C129825
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
FDA ORPHAN DRUG 311610
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
Code System Code Type Description
DRUG BANK
DB11763
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
PRIMARY
NCI_THESAURUS
C88311
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
PRIMARY
INN
9480
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
PRIMARY
FDA UNII
6O01GMS00P
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
PRIMARY
PUBCHEM
25062766
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
PRIMARY
WIKIPEDIA
CYT387
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
PRIMARY
ChEMBL
CHEMBL1078178
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
PRIMARY
CAS
1056634-68-4
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
PRIMARY
EVMPD
SUB177206
Created by admin on Fri Jun 25 22:28:07 UTC 2021 , Edited by admin on Fri Jun 25 22:28:07 UTC 2021
PRIMARY
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