BMS-911543

Investigational

Details

Stereochemistry	ACHIRAL
Molecular Formula	C23H28N8O
Molecular Weight	432.5214
Optical Activity	NONE
Defined Stereocenters	0 / 0
E/Z Centers	0
Charge	0

SHOW SMILES / InChI

Structure Search

SMILES

CCN1C(=CC2=C1N=C(NC3=NN(C)C(C)=C3)C4=C2N(C)C=N4)C(=O)N(C5CC5)C6CC6

InChI

InChIKey=JCINBYQJBYJGDM-UHFFFAOYSA-N

InChI=1S/C23H28N8O/c1-5-30-17(23(32)31(14-6-7-14)15-8-9-15)11-16-20-19(24-12-28(20)3)21(26-22(16)30)25-18-10-13(2)29(4)27-18/h10-12,14-15H,5-9H2,1-4H3,(H,25,26,27)

HIDE SMILES / InChI

Molecular Formula	C23H28N8O
Molecular Weight	432.5214
Charge	0
Count

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

Description
Sources: https://www.ncbi.nlm.nih.gov/pubmed/26575024
Curator's Comment: description was created based on several sources, including https://www.ncbi.nlm.nih.gov/pubmed/26288683 | https://www.ncbi.nlm.nih.gov/pubmed/22015772

BMS 911543 is a selective orally administered small molecule inhibitor of Janus kinase 2 (JAK2), developed by BristolMyers Squibb for the myelofibrosis treatment. BMS 911543 displayed potent antiproliferative effects in mutated JAK2expressing cell lines. A superior antiproliferative response occurred in primary progenitor cells isolated from patients with JAK2positive myeloproliferative disease (MPD) compared with those isolated from healthy volunteers. In vivo, a single oral dose of BMS 911543 resulted in durable JAK2phosphorylated STAT signalling pathway inhibition in multiple species. In a JAK2expressing xenograft model (SET2), BMS 911543 displayed a minimally effective dose of <2 mg/kg on phosphorylated STAT5 pathway inhibition.

Originator

Approval Year

Targets

Primary Target	Pharmacology	Condition	Potency
Tyrosine-protein kinase JAK2 55 Target ID: CHEMBL2971 Sources: https://www.ncbi.nlm.nih.gov/pubmed/22015772	Inhibitor 8297		0.48 nM [Ki]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Cancer 592 Sources: https://clinicaltrials.gov/ct2/show/NCT01236352	Primary		Phase II 1132	Unknown Approved Use Unknown

C_max

Value	Dose	Co-administered	Analyte	Population
162340 nM EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25912019	30 mg/kg single, oral dose: 30 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		BMS-911543 plasma	Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

AUC

Value	Dose	Co-administered	Analyte	Population
1092620 nM × h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/25912019	30 mg/kg single, oral dose: 30 mg/kg route of administration: Oral experiment type: SINGLE co-administered:		BMS-911543 plasma	Mus musculus population: UNKNOWN age: ADULT sex: UNKNOWN food status: UNKNOWN

T_1/2

Value	Dose	Co-administered	Analyte	Population
4.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26225254	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:		BMS-911543 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

F_unbound

Value	Dose	Co-administered	Analyte	Population
2% EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/26225254	240 mg single, oral dose: 240 mg route of administration: Oral experiment type: SINGLE co-administered:		BMS-911543 plasma	Homo sapiens population: UNHEALTHY age: ADULT sex: FEMALE / MALE food status: UNKNOWN

Doses

Dose	Population	Adverse events
200 mg 2 times / day multiple, oral MTD Dose: 200 mg, 2 times / day Route: oral Route: multiple Dose: 200 mg, 2 times / day Sources: https://www.researchgate.net/publication/336490176_BMS-911543_A_Selective_JAK2_Inhibitor_A_Multicenter_Phase_12a_Study_In_Myelofibrosis	unhealthy, ADULT Health Status: unhealthy Condition: cancer Age Group: ADULT Sex: M+F Food Status: UNKNOWN Sources: https://www.researchgate.net/publication/336490176_BMS-911543_A_Selective_JAK2_Inhibitor_A_Multicenter_Phase_12a_Study_In_Myelofibrosis	Sources: https://www.researchgate.net/publication/336490176_BMS-911543_A_Selective_JAK2_Inhibitor_A_Multicenter_Phase_12a_Study_In_Myelofibrosis

Sourcing

Vendor/Aggregator	ID	URL
001 Chemical	DY428216	https://www.001chemical.com/chem/search?q=DY428216
1PlusChem LLC	1P000X4H	https://www.1pchem.com/search?query=1P000X4H
AChemBlock	M15448	http://www.achemblock.com/catalogsearch/result/?q=M15448
AK Scientific	SYN5730	https://aksci.com/item_detail.php?cat=SYN5730
AOBIOUS INC	AOB87390	http://aobious.com/aobious/search?search_query=AOB87390
Angene	AGN-PC-0WCTJD	http://www.angenechemical.com/productshow/AGN-PC-0WCTJD.html
ApexBio Technology	A4152	https://www.apexbt.com/catalogsearch/result/?q=A4152
AstaTech	42179	http://astatechinc.com/CPSResult.php?CRNO=42179
BLD Pharm	BD328703	http://www.bldpharm.com/search/Search.html?keyword=BD328703
BOC Sciences	1271022-90-2	http://www.bocsci.com/description.asp?cas=1271022-90-2
Cayman Chemical	21088	http://www.caymanchem.com/app/template/Product.vm/catalog/21088
Chem Scene	CS-3237	http://www.chemscene.com/goproductList/searchProductList?productObj=CS-3237
ChemShuttle	131688	https://www.chemshuttle.com/catalogsearch/result/?q=131688
Excenen	EX-A1551	http://www.excenen.com/searchresultlist.php?id=EX-A1551
KeyOrganics	AS-17031	http://www.keyorganicsinc.com/bionet/catalogsearch/result?q=AS-17031
Matrix Scientific	152580	http://www.matrixscientific.com/152580.html
MedChem Express	HY-15270	https://www.medchemexpress.com/search.html?q=HY-15270&ft=&fa=&fp=
MolPort	MolPort-044-181-475	https://www.molport.com/shop/molecule-link/MolPort-044-181-475
Molcore	MC428216	http://www.molcore.com/CatMC428216.html
Molnova	M11136	https://www.molnova.com/en/serch-list.html?keywords=M11136
MuseChem	I001084	https://www.musechem.com/product/I001084.html
Selleck Chemicals	S7144	http://www.selleckchem.com/search.html?searchDTO.searchParam=S7144
ShangHai Biochempartner	BCP07258	http://www.biochempartner.com/search_BCP07258
TargetMol	T6790	https://www.targetmol.com/search?keyword=T6790
Toronto Research Chemicals	B596075	https://www.trc-canada.com/product-detail/?CatNum=B596075
Toronto Research Chemicals	H956180	https://www.trc-canada.com/product-detail/?CatNum=H956180
eMolecules	193590673	https://orderbb.emolecules.com/search/#?query=193590673
eMolecules	48876547	https://orderbb.emolecules.com/search/#?query=48876547
eMolecules	50550715	https://orderbb.emolecules.com/search/#?query=50550715
eNovation Chemicals	D501969	https://www.enovationchem.com/Products.asp?SEARCHTEXT=D501969&searchbtn.x=0&searchbtn.y=0
mcule	MCULE-5609924069	https://mcule.com/MCULE-5609924069/

PubMed

Title	Date	PubMed
Characterization of BMS-911543, a functionally selective small-molecule inhibitor of JAK2.	2012 Feb	22015772

Patents

Sample Use Guides

In Vivo Use Guide

The Brca1-KPC mice( 5–6 weeks of age, with a pancreatic mass of approximately 50–100 mm3) were treated for 2 weeks by daily oral gavage at a dose of 30 mg/kg BMS-911543. BMS-911543 treated mice had an overall reduction in bioluminescent imaging signal as compared to the vehicle controls

Route of Administration: Oral

In Vitro Use Guide

Human and murine pancreatic ductal adenocarcinoma (PDAC) tumor cells were treated with BMS-911543 or DMSO vehicle control for 48 hours. Treatment of murine or human PDAC cell lines in vitro with BMS-911543 decreased proliferation only at concentrations greater than 20 mkM.

Substance Class	Chemical Created by `admin` on `Sat Dec 16 05:00:26 GMT 2023` Edited by `admin` on `Sat Dec 16 05:00:26 GMT 2023`
Record UNII	7N03P021J8
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

BMS-911543

Common Name

English

IMIDAZO(4,5-D)PYRROLO(2,3-B)PYRIDINE-7-CARBOXAMIDE, N,N-DICYCLOPROPYL-4-((1,5-DIMETHYL-1H-PYRAZOL-3-YL)AMINO)-6-ETHYL-1,6-DIHYDRO-1-METHYL-

Systematic Name

English

JAK2 INHIBITOR BMS-911543

Code

English

Classification Tree Code System Code

NCI_THESAURUS

C129825