Momelotinib dihydrochloride monohydrate

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H22N6O2.2ClH.H2O
Molecular Weight	505.397
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure of Momelotinib dihydrochloride monohydrate

Structure Search

SMILES

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

InChI

InChIKey=RQKCPSIFARJBOR-UHFFFAOYSA-N

InChI=1S/C23H22N6O2.2ClH.H2O/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;1H2

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

Molecular Formula	H2O
Molecular Weight	18.0153
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
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
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

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 `Sat Dec 16 18:54:41 GMT 2023` Edited by `admin` on `Sat Dec 16 18:54:41 GMT 2023`
Record UNII	LDX8893L5D
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

Momelotinib dihydrochloride monohydrate

Common Name

English

CYT-387 DIHYDROCHLORIDE MONOHYDRATE

Code

English

MOMELOTINIB HYDROCHLORIDE HYDRATE

Common Name

English

Benzamide, N-(cyanomethyl)-4-[2-[[4-(4-morpholinyl)phenyl]amino]-4-pyrimidinyl]-, hydrochloride, hydrate (1:2:1)

Systematic Name

English

CYT-11387 DIHYDROCHLORIDE MONOHYDRATE

Code

English

MOMELOTINIB HYDROCHLORIDE HYDRATE [JAN]

Common Name

English

OJJAARA

Brand Name

English

Code System Code Type Description

PUBCHEM

102514733