| Size | Price | Stock | Qty |
|---|---|---|---|
| 2mg |
|
||
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| Other Sizes |
|
Purity: ≥98%
BMS-911543 (BMS911543) is a potent, selective and orally bioavailable inhibitor of JAK2 (Janus-associated kinase) with potential anticancer activity. It inhibits JAK2 with an IC50 of 1.1 nM, and shows ~350-, 75- and 65-fold selectivity over JAK1, JAK3 and TYK2, respectively. BMS-911543 also demonstrated potent anti-proliferative effects with IC50 values of 60 and 70nM in JAK-dependent cells SET2 and Ba/F3, respectively.
| ln Vitro |
At IC50s of 1.1 nM, BMS-911543 exhibits selectivity against JAK2, but is less selective against JAK1, JAK3, and TYK2 (IC50 values of 75, 360, and 66 nM, respectively). PDE4 has an IC50 of 5.6 μM, while BMS-911543 exhibits an IC50 of >25 μM for all targets. The JAK2 pathway-dependent SET-2 and BaF3-V617F engineered cell lines show a strong antiproliferative effect to BMS-911543, with IC50s of 60 and 70 nM, respectively. This effect is correlated with similar activity on constitutively active pSTAT5, with IC50s of 80 and 65 nM, respectively][1]. PDAC cell lines from humans or mice are cytotoxically affected by BMS-911543 (>20 μM). T regulatory cell differentiation is likewise inhibited in vitro by BMS-911543 at 5 and 10 μM[2].
|
||
|---|---|---|---|
| ln Vivo |
In both rats (mean AUC0-72 h, 11300 μM·h) and dogs (AUC0-24 h, 610 μM·h), BMS-911543 is well tolerated up to 100 mg/kg. In two-week repeat dose experiments in rats, a 15 mg/kg/day dose (Day 14 AUC0-24 h, 3200 μM·h) is well tolerated[1]. In KPC -Brca1 mice, BMS-911543 (30 mg/kg, po) inhibits tumor growth and increases median survival. BMS-911543 also specifically lowers intratumoral FoxP3+ T regulatory cell counts in mice treated with it, as well as pSTAT5 expression in pancreatic tumors[2].
|
||
| Animal Protocol |
|
||
| References |
[1]. Wan H, et al. Discovery of a Highly Selective JAK2 Inhibitor, BMS-911543, for the Treatment of Myeloproliferative Neoplasms. ACS Med Chem Lett. 2015 Jul 12;6(8):850-5.
[2]. Mace TA, et al. Single agent BMS-911543 Jak2 inhibitor has distinct inhibitory effects on STAT5 signaling in genetically engineered mice with pancreatic cancer. Oncotarget. 2015 Dec 29;6(42):44509-22 |
| Molecular Formula |
C23H28N8O
|
|
|---|---|---|
| Molecular Weight |
432.52
|
|
| CAS # |
1271022-90-2
|
|
| Related CAS # |
|
|
| SMILES |
O=C(C1=C([H])C2=C3C(=C(N([H])C4C([H])=C(C([H])([H])[H])N(C([H])([H])[H])N=4)N=C2N1C([H])([H])C([H])([H])[H])N=C([H])N3C([H])([H])[H])N(C1([H])C([H])([H])C1([H])[H])C1([H])C([H])([H])C1([H])[H]
|
|
| Chemical Name |
N,N-dicyclopropyl-4-((1,5-dimethyl-1H-pyrazol-3-yl)amino)-6-ethyl-1-methyl-1,6-dihydroimidazo[4,5-d]pyrrolo[2,3-b]pyridine-7-carboxamide
|
|
| Synonyms |
|
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
|
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
|
|||
|---|---|---|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (5.78 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (5.78 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3120 mL | 11.5602 mL | 23.1203 mL | |
| 5 mM | 0.4624 mL | 2.3120 mL | 4.6241 mL | |
| 10 mM | 0.2312 mL | 1.1560 mL | 2.3120 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT01236352 | Terminated Has Results |
Drug: BMS-911543 | Cancer | Bristol-Myers Squibb | April 7, 2011 | Phase 1 Phase 2 |
Differential inhibitory sensitivity of JAK2V617F in vivo.Leukemia.2012Feb;26(2):280-8. |
Effects of BMS-911543 on cytokine-dependent and -independent hematopoietic colony growth of MPN patients with activating JAK2 pathway mutations.Leukemia.2012Feb;26(2):280-8. |
Effects of BMS-911543 in a mouse model of immunosuppression.Leukemia.2012Feb;26(2):280-8.
Regulation of STAT1 as part of a JAK2-mediated transcriptional program. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
