MOMELOTINIB

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

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	MOL RATIO 1 MOL RATIO (average)

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

Description

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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase JAK1 38	Inhibitor 8,297		11.0 nM [IC50]
Tyrosine-protein kinase JAK2 55	Inhibitor 8,297		18.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Pancreatic cancer 97	Primary	Phase III 656	Unknown
Non-small cell lung cancer 206	Primary	Phase I 428	Unknown
Secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia) 3	Primary	Phase III 656	Unknown
Primary myelofibrosis 7	Primary	Phase III 656	Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1,737	substrate 1,037

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1,461	CYP2C8 693 BCRP 561 CYP2C19 991 CYP1A2 1,054 P-gp 1,537 AO 16

Drug as perpetrator

Show entries

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1,650	inhibitor 3,277	yes [IC50 5.8048 uM]

Showing 1 to 1 of 1 entries

Previous1Next

Drug as victim

Show entries

Target	Modality	Activity
CYP2C19 991	substrate 3,367	major
AO 16	substrate 3,367	yes
BCRP 561	substrate 3,367	yes
CYP1A2 1,054	substrate 3,367	yes
CYP2C8 693	substrate 3,367	yes

Showing 1 to 5 of 8 entries

Previous1 2Next

Sourcing

Sourcing

Show entries

Vendor/Aggregator	ID	URL
001 Chemical	DY114429	https://www.001chemical.com/chem/search?q=DY114429
001 Chemical	DY34203	https://www.001chemical.com/chem/search?q=DY34203
1PlusChem LLC	1P0038PG	https://www.1pchem.com/search?query=1P0038PG
1PlusChem LLC	1P008TVX	https://www.1pchem.com/search?query=1P008TVX
A2B Chem	AB50452	http://a2bchem.com/prod/AB50452

Showing 1 to 5 of 59 entries

Previous1 2 3 4 5…12Next

PubMed

Show entries

Title	Date	PubMed
		252160359
CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms.	2010 Jun 24	20385788
The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells.	2011 Dec	21788946
Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis.	2013 Jun	23459451
P-glycoprotein (MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) restrict brain accumulation of the JAK1/2 inhibitor, CYT387.	2013 Oct	23827160

Showing 1 to 5 of 9 entries

Previous1 2Next

Patents

Sample Use Guides

In Vivo Use Guide

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

In Vitro Use Guide

0.5 and 1.5 uM CYT387 caused growth suppression and apoptosis in JAK2-dependent hematopoietic cell lines, while nonhematopoietic cell lines were unaffected.