Home JAK/STAT JAK inhibitor BMS-911543 For research use only.

BMS-911543

BMS-911543 is a potent and selective inhibitor of JAK2 with IC50 of 1.1 nM, ~350-, 75- and 65-fold selective to JAK1, JAK3 and TYK2, respectively. Phase 1/2.

BMS-911543 Chemical Structure

BMS-911543 Chemical Structure

CAS No. 1271022-90-2

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BMS-911543 Related Products

Signaling Pathway

JAK Signaling Pathways

JAK Signaling Pathway

Biological Activity

Description BMS-911543 is a potent and selective inhibitor of JAK2 with IC50 of 1.1 nM, ~350-, 75- and 65-fold selective to JAK1, JAK3 and TYK2, respectively. Phase 1/2.
Targets
JAK2 [1]
(Cell-free assay)		 SET-2 [1]
(Cell-free assay)		 TYK2 [1]
(Cell-free assay)		 JAK3 [1]
(Cell-free assay)
1.1 nM 60 nM 66 nM 75 nM
In vitro
In vitro BMS-911543 shows potent antiproliferative activity in the SET-2 as well as BaF3-V617F engineered cell lines (both dependent upon JAK2 pathway), with IC50 values of 60 and 70 nM, respectively. The antiproliferative activity of BMS-911543 in SET-2 and BaF3-V617F cells correlates with similar activity on constitutively active pSTAT5 (IC50 80 and 65 nM, respectively). In contrast, non-JAK2-dependent cell lines (A549, MDA-MB-231, MiaPaCa-2) are significantly less sensitive to the inhibitor treatment. The excellent biochemical selectivity versus JAK1/3 translates to good cellular and functional selectivity in an IL-2 mediated T-cell proliferation assay (IC50 990 nM). Also, cell lines that rely on other JAK family members, including CTLL2 and parental BaF3 cells stimulated with IL-3, shows weak antiproliferative activity for BMS-911543 (IC50 2.9 and 3.5 μM, respectively)[1].
In Vivo
In vivo BMS-911543 suppresses the pSTAT5 levels (mediated by wild type JAK2) relative to vehicle control when stimulated with thrombopoetin (TPO) in a mouse pharmacodynamic model. The responses are dose dependent and results in nearly complete normalization of pSTAT5 levels for 18 h at the highest oral dose of 30 mg/kg. At an intermediate 10 mg/kg oral dose, ∼65% reduction is observed up to 18 h, whereas at the 5 mg/kg dose, approximately 50% reduction in pSTAT5 for 8 h is achieved. Observed pSTAT5 reductions correlates with exposures of BMS-911543, with AUC0–8h values of 23, 41, and 109 μM·h, respectively, for dose levels of 5, 10, and 30 mg/kg. In addition, BMS-911543 demonstrates a potent and sustained (2 mg/kg up to 7 h) PD effect in blocking pSTAT5 formation in mice grafted with human SET-2 cells harboring JAK2-V617F mutation. The absolute oral bioavailability in solution is >50% in mice, rats, dogs, and monkeys. In addition, the absorption of BMS-911543 is not significantly impacted by particle dissolution (suspension formulation), with a relative bioavailability (vs solution) of ∼60% in rats and ∼100% in dogs[1].
Animal Research Animal Models BALB/c mice
Dosages 10 mg/kg
Administration by oral gavage
NCT Number Recruitment Conditions Sponsor/Collaborators Start Date Phases
NCT01236352 Terminated
Cancer
Bristol-Myers Squibb
 April 7 2011 Phase 1|Phase 2

Chemical Information & Solubility

Molecular Weight 432.52 Formula

C23H28N8O
CAS No. 1271022-90-2 SDF Download BMS-911543 SDF
Smiles CCN1C(=CC2=C3C(=C(N=C21)NC4=NN(C(=C4)C)C)N=CN3C)C(=O)N(C5CC5)C6CC6
Storage (From the date of receipt)

In vitro
Batch:

DMSO : 35 mg/mL ( (80.92 mM) Moisture-absorbing DMSO reduces solubility. Please use fresh DMSO.)

Ethanol : 33 mg/mL

Water : Insoluble


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In vivo
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Tech Support

Answers to questions you may have can be found in the inhibitor handling instructions. Topics include how to prepare stock solutions, how to store inhibitors, and issues that need special attention for cell-based assays and animal experiments.

Handling Instructions

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