Powder: -20°C for 3 years | In solvent: -80°C for 1 year
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.
Pack Size | Availability | Price/USD | Quantity |
---|---|---|---|
1 mg | In stock | $ 51.00 | |
2 mg | In stock | $ 72.00 | |
5 mg | In stock | $ 117.00 | |
10 mg | In stock | $ 192.00 | |
25 mg | In stock | $ 396.00 | |
50 mg | In stock | $ 593.00 | |
1 mL * 10 mM (in DMSO) | In stock | $ 113.00 |
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&IC50 | TYK2:75nM, AK1:1.1 nM, JAK3:350nM |
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 | 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]. |
Synonyms | BMS911543 |
Molecular Weight | 432.52 |
Formula | C23H28N8O |
CAS No. | 1271022-90-2 |
Powder: -20°C for 3 years | In solvent: -80°C for 1 year
DMSO: 34 mg/mL (78.6 mM)
Ethanol: 21 mg/mL (48.6 mM)
H2O: < 1 mg/mL (insoluble or slightly soluble)
You can also refer to dose conversion for different animals. More
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BMS-911543 1271022-90-2 Angiogenesis Chromatin/Epigenetic JAK/STAT signaling Stem Cells Tyrosine Kinase/Adaptors Tyrosine Kinases JAK Histone Methyltransferase BMS 911543 Janus kinase inhibit Inhibitor BMS911543 inhibitor