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Details

Stereochemistry ACHIRAL
Molecular Formula C23H28N8O
Molecular Weight 432.5223
Optical Activity NONE
Defined Stereocenters 0 / 0
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of BMS-911543

SMILES

CCn1c(cc2c3c(c(N=c4cc(C)n(C)[nH]4)nc21)ncn3C)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 432.5223
Charge 0
Count
Stereochemistry ACHIRAL
Additional Stereochemistry No
Defined Stereocenters 0 / 0
E/Z Centers 0
Optical Activity NONE

Description
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.

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
0.48 nM [Ki]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Unknown

Approved Use

Unknown
Cmax

Cmax

ValueDoseCo-administeredAnalytePopulation
162340 nM
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

AUC

ValueDoseCo-administeredAnalytePopulation
1092620 nM × h
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
T1/2

T1/2

ValueDoseCo-administeredAnalytePopulation
4.9 h
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
Funbound

Funbound

ValueDoseCo-administeredAnalytePopulation
2%
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

Doses

DosePopulationAdverse events​
200 mg 2 times / day multiple, oral
MTD
unhealthy, ADULT
Health Status: unhealthy
Condition: cancer
Age Group: ADULT
Sex: M+F
Food Status: UNKNOWN
Sources:
Sourcing

Sourcing

Vendor/AggregatorIDURL
PubMed

PubMed

TitleDatePubMed
Characterization of BMS-911543, a functionally selective small-molecule inhibitor of JAK2.
2012 Feb
Patents

Sample Use Guides

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
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 Jun 26 10:36:43 UTC 2021
Edited
by admin
on Sat Jun 26 10:36:43 UTC 2021
Record UNII
7N03P021J8
Record Status Validated (UNII)
Record Version
  • Download
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
Created by admin on Sat Jun 26 10:36:43 UTC 2021 , Edited by admin on Sat Jun 26 10:36:43 UTC 2021
NCI_THESAURUS C125450
Created by admin on Sat Jun 26 10:36:43 UTC 2021 , Edited by admin on Sat Jun 26 10:36:43 UTC 2021
Code System Code Type Description
NCI_THESAURUS
C95702
Created by admin on Sat Jun 26 10:36:43 UTC 2021 , Edited by admin on Sat Jun 26 10:36:43 UTC 2021
PRIMARY
DRUG BANK
DB12591
Created by admin on Sat Jun 26 10:36:43 UTC 2021 , Edited by admin on Sat Jun 26 10:36:43 UTC 2021
PRIMARY
CAS
1271022-90-2
Created by admin on Sat Jun 26 10:36:43 UTC 2021 , Edited by admin on Sat Jun 26 10:36:43 UTC 2021
PRIMARY
PUBCHEM
50922691
Created by admin on Sat Jun 26 10:36:43 UTC 2021 , Edited by admin on Sat Jun 26 10:36:43 UTC 2021
PRIMARY
EPA CompTox
1271022-90-2
Created by admin on Sat Jun 26 10:36:43 UTC 2021 , Edited by admin on Sat Jun 26 10:36:43 UTC 2021
PRIMARY
ChEMBL
CHEMBL3545215
Created by admin on Sat Jun 26 10:36:43 UTC 2021 , Edited by admin on Sat Jun 26 10:36:43 UTC 2021
PRIMARY
FDA UNII
7N03P021J8
Created by admin on Sat Jun 26 10:36:43 UTC 2021 , Edited by admin on Sat Jun 26 10:36:43 UTC 2021
PRIMARY
Related Record Type Details
TARGET -> INHIBITOR
TARGET -> INHIBITOR
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ACTIVE MOIETY