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Technical Data
| Formula | C23H28N8O |
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| Molecular Weight | 432.52 | CAS No. | 1271022-90-2 | |
| Solubility (25°C)* | In vitro | DMSO | 35 mg/mL (80.92 mM) | |
| Ethanol | 33 mg/mL (76.29 mM) | |||
| Water | Insoluble | |||
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* <1 mg/ml means slightly soluble or insoluble. * Please note that Selleck tests the solubility of all compounds in-house, and the actual solubility may differ slightly from published values. This is normal and is due to slight batch-to-batch variations. * Room temperature shipping (Stability testing shows this product can be shipped without any cooling measures.) |
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Preparing Stock Solutions
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. | ||||||||
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| 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]. |
Protocol (from reference)
| Animal Study:[1] |
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Selleck's BMS-911543 has been cited by 6 publications
| Novel JAK Inhibitors to Reduce Graft-Versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation in a Preclinical Mouse Model [ Molecules, 2024, 29(8)1801] | PubMed: 38675621 |
| IL-6/JAK2-dependent G6PD phosphorylation promotes nucleotide synthesis and supports tumor growth [ Mol Metab, 2023, 10.1016/j.molmet.2023.101836] | PubMed: 37949355 |
| Acquired JAK2 mutations confer resistance to JAK inhibitors in cell models of acute lymphoblastic leukemia [ NPJ Precis Oncol, 2021, 5(1):75] | PubMed: 34376782 |
| Quantitative proteomics analysis identifies MUC1 as an effect sensor of EGFR inhibition. [ Oncogene, 2019, 38(9):1477-1488] | PubMed: 30305724 |
| MAPK pathway activity plays a key role in PD-L1 expression of lung adenocarcinoma cells [ J Pathol, 2019, 10.1002/path.5280] | PubMed: 30972766 |
| Mechanism and prognostic value of indoleamine 2,3-dioxygenase 1 expressed in hepatocellular carcinoma [Li S Cancer Sci, 2018, 109(12):3726-3736] | PubMed: 30264546 |
RETURN POLICY
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SHIPPING AND STORAGE
Selleck products are transported at room temperature. If you receive the product at room temperature, please rest assured, the Selleck Quality Inspection Department has conducted experiments to verify that the normal temperature placement of one month will not affect the biological activity of powder products. After collecting, please store the product according to the requirements described in the datasheet. Most Selleck products are stable under the recommended conditions.
NOT FOR HUMAN, VETERINARY DIAGNOSTIC OR THERAPEUTIC USE.