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

Structure Search

SMILES

O=C(NCC#N)C1=CC=C(C=C1)C2=CC=NC(NC3=CC=C(C=C3)N4CCOCC4)=N2

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

Description
Sources: http://adisinsight.springer.com/drugs/800030557
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

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase JAK1 39 Target ID: CHEMBL2835 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19295546	Inhibitor 8504		11.0 nM [IC50]
Tyrosine-protein kinase JAK2 59 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19295546	Inhibitor 8504		18.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Pancreatic cancer 98 Sources: http://adisinsight.springer.com/drugs/800030557	Primary	Phase III 665	Unknown Approved Use Unknown
Non-small cell lung cancer 211 Sources: http://adisinsight.springer.com/drugs/800030557	Primary	Phase I 438	Unknown Approved Use Unknown
Secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia) 3 Sources: http://adisinsight.springer.com/drugs/800030557	Primary	Phase III 665	Unknown Approved Use Unknown
Primary myelofibrosis 10 Sources: http://adisinsight.springer.com/drugs/800030557	Primary	Phase III 665	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
1860 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29311136	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		MOMELOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
16327 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29311136	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		MOMELOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29311136	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		MOMELOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
19.2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/29311136	200 mg single, oral dose: 200 mg route of administration: Oral experiment type: SINGLE co-administered:		MOMELOTINIB plasma	Homo sapiens population: HEALTHY age: ADULT sex: MALE food status: UNKNOWN

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1946	substrate 1193

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1741	CYP2C8 810 BCRP 697 CYP2C19 1119 CYP1A2 1197 P-gp 2052

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677153	yes [IC50 5.8048 uM]

Drug as victim

Target	Modality	Activity
CYP2C19 1119	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29311136/	major
BCRP 697	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23827160/	yes
CYP1A2 1197	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29311136/	yes
CYP2C8 810	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29311136/	yes
CYP2C9 1193	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29311136/	yes
CYP3A4 1946	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/29311136/	yes
P-gp 2052	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/23827160/	yes

Sourcing

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
AbovChem LLC	HY-10963	http://www.abovchem.com/pc/en/product_list.aspx?wd=HY-10963
Aceschem	ACS019859	https://www.aceschem.com/catalog/search.do?q=ACS019859
AChemBlock	L14955	http://www.achemblock.com/catalogsearch/result/?q=L14955
Achemo Scientific Limited	AC-95599	http://www.achemo.com/search/?Keyword=AC-95599
AK Scientific	X7506	https://aksci.com/item_detail.php?cat=X7506
Angene	AGN-PC-04YXR0	http://www.angenechemical.com/productshow/AGN-PC-04YXR0.html
Angene	AGN-PC-0WD7JW	http://www.angenechemical.com/productshow/AGN-PC-0WD7JW.html
AOBIOUS INC	AOB4616	http://aobious.com/aobious/search?search_query=AOB4616
ApexBio Technology	A3339	https://www.apexbt.com/catalogsearch/result/?q=A3339
ApexBio Technology	A4143	https://www.apexbt.com/catalogsearch/result/?q=A4143
AstaTech	41252	http://astatechinc.com/CPSResult.php?CRNO=41252
Axon MedChem	1681	https://www.axonmedchem.com/product/1681
BLD Pharm	BD629869	http://www.bldpharm.com/search/Search.html?keyword=BD629869
BLD Pharm	BD629870	http://www.bldpharm.com/search/Search.html?keyword=BD629870
Capot Chemical	33983	https://www.capotchem.com/search.do?q=33983
Cayman Chemical	16246	http://www.caymanchem.com/app/template/Product.vm/catalog/16246
Chem Scene	CS-0053	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0053
Chem Scene	CS-0765	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-0765
ChemShuttle	111935	https://www.chemshuttle.com/catalogsearch/result/?q=111935
eMolecules	31507583	https://orderbb.emolecules.com/search/#?query=31507583
eMolecules	44811542	https://orderbb.emolecules.com/search/#?query=44811542
eMolecules	50285372	https://orderbb.emolecules.com/search/#?query=50285372
eMolecules	89939472	https://orderbb.emolecules.com/search/#?query=89939472
eNovation Chemicals	D572852	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D572852&searchbtn.x=0&searchbtn.y=0
Excenen	EX-A260	http://www.excenen.com/searchresultlist.php?id=EX-A260
Hairui	MOXM012	http://www.hairuichem.com/en/product/search.do?q=MOXM01206
Hairui	MOXM01206	http://www.hairuichem.com/en/product/search.do?q=MOXM01206
KeyOrganics	AS-19389	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-19389
Lab Seeker	SC-94176	http://www.labseeker.com/search.php?keywords=SC-94176&category=0
LabSeeker	SC-94176	http://www.labseeker.com/search.php?keywords=SC-94176&category=0
Matrix Scientific	95905	http://www.matrixscientific.com/095905.html
mcule	MCULE-1744740651	https://mcule.com/MCULE-1744740651/
mcule	MCULE-7493518071	https://mcule.com/MCULE-7493518071/
mcule	MCULE-7598987545	https://mcule.com/MCULE-7598987545/
MedChem Express	HY-10961	https://www.medchemexpress.com/search.html?q=HY-10961&ft=&fa=&fp=
MedChem Express	HY-10962	https://www.medchemexpress.com/search.html?q=HY-10962&ft=&fa=&fp=
Molcore	MC114429	http://www.molcore.com/CatMC114429.html
Molcore	MC34203	http://www.molcore.com/CatMC34203.html
Molnova	M10259	https://www.molnova.com/en/serch-list.html?keywords=M10259
Molnova	M10260	https://www.molnova.com/en/serch-list.html?keywords=M10260
Molnova	M10261	https://www.molnova.com/en/serch-list.html?keywords=M10261
MolPort	MolPort-016-633-319	https://www.molport.com/shop/molecule-link/MolPort-016-633-319
MolPort	MolPort-046-416-873	https://www.molport.com/shop/molecule-link/MolPort-046-416-873
MuseChem	I000293	https://www.musechem.com/product/I000293.html
PI Chemicals	PI-38459	http://www.pipharm.com/catalog_products/PI-38459.html
Ryan Scientific	PLX647	https://ryansci.com/products?q=PLX647&list_q=&search_type=exact
Selleck Chemicals	S2219	http://www.selleckchem.com/search.html?searchDTO.searchParam=S2219
ShangHai Biochempartner	BCP000310	http://www.biochempartner.com/search_BCP000310
ShangHai Biochempartner	BCP02328	http://www.biochempartner.com/search_BCP02328
ShangHai Biochempartner	BCP12875	http://www.biochempartner.com/search_BCP12875
Synovel	SN-0430	http://www.synovellab.com/?s=SN-0430&submit=Search
TargetMol	T1849	https://www.targetmol.com/search?keyword=T1849
Toronto Research Chemicals	C991800	https://www.trc-canada.com/product-detail/?CatNum=C991800
Toronto Research Chemicals	M305703	https://www.trc-canada.com/product-detail/?CatNum=M305703

PubMed

Title	Date	PubMed
Momelotinib in myelofibrosis: JAK1/2 inhibitor with a role in treating and understanding the anemia.	2017-02	27785927
A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis.	2017-01	27634203
Momelotinib treatment-emergent neuropathy: prevalence, risk factors and outcome in 100 patients with myelofibrosis.	2015-04	25511866
Inhibition of the JAK2/STAT3 pathway in ovarian cancer results in the loss of cancer stem cell-like characteristics and a reduced tumor burden.	2014-05-06	24886434
Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit.	2014-04	24444711
P-glycoprotein (MDR1/ABCB1) and breast cancer resistance protein (BCRP/ABCG2) restrict brain accumulation of the JAK1/2 inhibitor, CYT387.	2013-10	23827160
Safety and efficacy of CYT387, a JAK1 and JAK2 inhibitor, in myelofibrosis.	2013-06	23459451
The novel JAK inhibitor CYT387 suppresses multiple signalling pathways, prevents proliferation and induces apoptosis in phenotypically diverse myeloma cells.	2011-12	21788946
CYT387, a novel JAK2 inhibitor, induces hematologic responses and normalizes inflammatory cytokines in murine myeloproliferative neoplasms.	2010-06-24	20385788
Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs).	2009-10-15	19762238
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.	2009-08	19295546

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.

Name

Type

Language

CYT-0387

Preferred Name

English

MOMELOTINIB

Official Name

English

MOMELOTINIB [USAN]

Common Name

English

Momelotinib [WHO-DD]

Common Name

English

CYT387

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