Momelotinib Dihydrochloride

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H22N6O2.2ClH
Molecular Weight	487.382
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of Momelotinib Dihydrochloride

Structure Search

SMILES

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

InChI

InChIKey=IPNATXQRPWRHKD-UHFFFAOYSA-N

InChI=1S/C23H22N6O2.2ClH/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);2*1H

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

Molecular Formula	ClH
Molecular Weight	36.461
Charge	0
Count

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

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 38 Target ID: CHEMBL2835 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19295546	Inhibitor 8297		11.0 nM [IC50]
Tyrosine-protein kinase JAK2 55 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/19295546	Inhibitor 8297		18.0 nM [IC50]

Conditions

Condition	Modality	Highest Phase	Product
Pancreatic cancer 97 Sources: http://adisinsight.springer.com/drugs/800030557	Primary	Phase III 656	Unknown Approved Use Unknown
Non-small cell lung cancer 206 Sources: http://adisinsight.springer.com/drugs/800030557	Primary	Phase I 428	Unknown Approved Use Unknown
Secondary myelofibrosis (post-polycythemia vera and post-essential thrombocythemia) 3 Sources: http://adisinsight.springer.com/drugs/800030557	Primary	Phase III 656	Unknown Approved Use Unknown
Primary myelofibrosis 7 Sources: http://adisinsight.springer.com/drugs/800030557	Primary	Phase III 656	Unknown Approved Use Unknown

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
substrate 1737	substrate 1037

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
P-gp 1461	CYP2C8 693 BCRP 561 CYP2C19 991 CYP1A2 1054 P-gp 1537 AO 16

Drug as perpetrator

Target	Modality	Activity	Metabolite	Clinical evidence
P-gp 1650	inhibitor 3277 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=363677153	yes [IC50 5.8048 uM]

Drug as victim

Target	Modality	Activity
CYP2C19 991	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29311136/	major
AO 16	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29311136/	yes
BCRP 561	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/23827160/	yes
CYP1A2 1054	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29311136/	yes
CYP2C8 693	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29311136/	yes
CYP2C9 1037	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29311136/	yes
CYP3A4 1737	substrate 3367 Sources: https://pubmed.ncbi.nlm.nih.gov/29311136/	yes
P-gp 1537	substrate 3367 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
AChemBlock	L14955	http://www.achemblock.com/catalogsearch/result/?q=L14955
AK Scientific	X7506	https://aksci.com/item_detail.php?cat=X7506
AOBIOUS INC	AOB4616	http://aobious.com/aobious/search?search_query=AOB4616
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
Achemo Scientific Limited	AC-95599	http://www.achemo.com/search/?Keyword=AC-95599
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
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
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
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=
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
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
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
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
mcule	MCULE-1744740651	https://mcule.com/MCULE-1744740651/
mcule	MCULE-7493518071	https://mcule.com/MCULE-7493518071/
mcule	MCULE-7598987545	https://mcule.com/MCULE-7598987545/

PubMed

Title	Date	PubMed
		252160359
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	19295546
Phenylaminopyrimidines as inhibitors of Janus kinases (JAKs).	2009 Oct 15	19762238
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
Inhibition of KRAS-driven tumorigenicity by interruption of an autocrine cytokine circuit.	2014 Apr	24444711
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	24886434
Momelotinib treatment-emergent neuropathy: prevalence, risk factors and outcome in 100 patients with myelofibrosis.	2015 Apr	25511866
Momelotinib in myelofibrosis: JAK1/2 inhibitor with a role in treating and understanding the anemia.	2017 Feb	27785927
A phase 1/2, open-label study evaluating twice-daily administration of momelotinib in myelofibrosis.	2017 Jan	27634203

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.

Substance Class	Chemical Created by `admin` on `Fri Dec 15 16:54:58 UTC 2023` Edited by `admin` on `Fri Dec 15 16:54:58 UTC 2023`
Record UNII	RBH995N496
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Momelotinib Dihydrochloride

Official Name

English

MOMELOTINIB DIHYDROCHLORIDE [USAN]

Common Name

English

CYT-387 DIHYDROCHLORIDE

Code

English

Momelotinib dihydrochloride [WHO-DD]

Common Name

English

BENZAMIDE, N-(CYANOMETHYL)-4-(2-((4-(4-MORPHOLINYL)PHENYL)AMINO)-4-PYRIMIDINYL)-, HYDROCHLORIDE (1:2)

Systematic Name

English

BENZAMIDE, N-(CYANOMETHYL)-4-(2-((4-(4-MORPHOLINYL)PHENYL)AMINO)-4-PYRIMIDINYL)-, DIHYDROCHLORIDE

Common Name

English

CYT387 DIHYDROCHLORIDE

Code

English

Classification Tree Code System Code

EU-Orphan Drug

EU/3/11/888