BMS-911543
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MedKoo CAT#: 205767

CAS#: 1271022-90-2

Description: BMS-911543 is an orally available small molecule targeting a subset of Janus-associated kinase (JAK) with potential antineoplastic activity. JAK2 inhibitor BMS-911543 selectively inhibits JAK2, thereby preventing the JAK/STAT (signal transducer and activator of transcription) signaling cascade, including activation of STAT3. This may lead to an induction of tumor cell apoptosis and a decrease in cellular proliferation. JAK2, often upregulated or mutated in a variety of cancer cells, mediates STAT3 activation and plays a key role in tumor cell proliferation and survival.


Chemical Structure

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BMS-911543
CAS# 1271022-90-2

Theoretical Analysis

MedKoo Cat#: 205767
Name: BMS-911543
CAS#: 1271022-90-2
Chemical Formula: C23H28N8O
Exact Mass: 432.23861
Molecular Weight: 432.52142
Elemental Analysis: C, 63.87; H, 6.53; N, 25.91; O, 3.70

Price and Availability

Size Price Availability Quantity
10.0mg USD 450.0 2 weeks
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Synonym: BMS911543; BMS-911543; BMS 911543.

IUPAC/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

InChi Key: JCINBYQJBYJGDM-UHFFFAOYSA-N

InChi Code: 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)

SMILES Code: O=C(C1=CC2=C(N(C)C=N3)C3=C(NC4=NN(C)C(C)=C4)N=C2N1CC)N(C5CC5)C6CC6

Appearance: Solid powder

Purity: >98% (or refer to the Certificate of Analysis)

Shipping Condition: Shipped under ambient temperature as non-hazardous chemical. This product is stable enough for a few weeks during ordinary shipping and time spent in Customs.

Storage Condition: Dry, dark and at 0 - 4 C for short term (days to weeks) or -20 C for long term (months to years).

Solubility: Soluble in DMSO, not in water

Shelf Life: >5 years if stored properly

Drug Formulation: This drug may be formulated in DMSO

Stock Solution Storage: 0 - 4 C for short term (days to weeks), or -20 C for long term (months).

HS Tariff Code: 2934.99.9001

Product Data:

Biological target: BMS-911543 is a selective JAK2 inhibitor, with IC50s of 1.1 nM, less selective at JAK1, JAK3 and TYK2 (IC50, 75, 360, 66 nM, respectively).
In vitro activity: In cellular assays, BMS-911543 showed 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 correlated with similar activity on constitutively active pSTAT5 (IC50 80 and 65 nM, respectively). Reference: ACS Med Chem Lett. 2015 Aug 13; 6(8): 850–855. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4538448/
In vivo activity: BMS-911543 treated mice had an overall reduction in BLI signal as compared to the vehicle controls (Figure 2B). Consistent with BLI data, further histological analysis of pancreata from treated mice showed fewer foci of PDAC, with a shift toward PanIN lesions when compared to vehicle controls (Figure 2C–2D and Supplementary Figure S1). In addition, BMS-911543-treated mice had 35% fewer Ki67 positive cells as compared to vehicle treated animals (p = 0.023; Figure 2E–2F). Reference: Oncotarget. 2015 Dec 29; 6(42): 44509–44522. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4792572/

Solubility Data

Solvent Max Conc. mg/mL Max Conc. mM
Solubility
DMSO 25.0 57.8
DMF 30.0 69.36
DMF:PBS (pH 7.2) (1:1) 0.5 1.16
Ethanol 17.0 39.3

Preparing Stock Solutions

The following data is based on the product molecular weight 432.52142 Batch specific molecular weights may vary from batch to batch due to the degree of hydration, which will affect the solvent volumes required to prepare stock solutions.

Recalculate based on batch purity %
Concentration / Solvent Volume / Mass 1 mg 5 mg 10 mg
1 mM 1.15 mL 5.76 mL 11.51 mL
5 mM 0.23 mL 1.15 mL 2.3 mL
10 mM 0.12 mL 0.58 mL 1.15 mL
50 mM 0.02 mL 0.12 mL 0.23 mL
Formulation protocol: 1. Mace TA, Shakya R, Elnaggar O, Wilson K, Komar HM, Yang J, Pitarresi JR, Young GS, Ostrowski MC, Ludwig T, Bekaii-Saab T, Bloomston M, Lesinski GB. 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. doi: 10.18632/oncotarget.6332. PMID: 26575024; PMCID: PMC4792572. 2. Wan H, Schroeder GM, Hart AC, Inghrim J, Grebinski J, Tokarski JS, Lorenzi MV, You D, Mcdevitt T, Penhallow B, Vuppugalla R, Zhang Y, Gu X, Iyer R, Lombardo LJ, Trainor GL, Ruepp S, Lippy J, Blat Y, Sack JS, Khan JA, Stefanski K, Sleczka B, Mathur A, Sun JH, Wong MK, Wu DR, Li P, Gupta A, Arunachalam PN, Pragalathan B, Narayanan S, K C N, Kuppusamy P, Purandare AV. 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. doi: 10.1021/acsmedchemlett.5b00226. PMID: 26288683; PMCID: PMC4538448. 3. Mace TA, Shakya R, Elnaggar O, Wilson K, Komar HM, Yang J, Pitarresi JR, Young GS, Ostrowski MC, Ludwig T, Bekaii-Saab T, Bloomston M, Lesinski GB. 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. doi: 10.18632/oncotarget.6332. PMID: 26575024; PMCID: PMC4792572. 4. Pomicter AD, Eiring AM, Senina AV, Zabriskie MS, Marvin JE, Prchal JT, O'Hare T, Deininger MW. Limited efficacy of BMS-911543 in a murine model of Janus kinase 2 V617F myeloproliferative neoplasm. Exp Hematol. 2015 Jul;43(7):537-45.e1-11. doi: 10.1016/j.exphem.2015.03.006. Epub 2015 Apr 24. PMID: 25912019; PMCID: PMC4487517.
In vitro protocol: 1. Mace TA, Shakya R, Elnaggar O, Wilson K, Komar HM, Yang J, Pitarresi JR, Young GS, Ostrowski MC, Ludwig T, Bekaii-Saab T, Bloomston M, Lesinski GB. 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. doi: 10.18632/oncotarget.6332. PMID: 26575024; PMCID: PMC4792572. 2. Wan H, Schroeder GM, Hart AC, Inghrim J, Grebinski J, Tokarski JS, Lorenzi MV, You D, Mcdevitt T, Penhallow B, Vuppugalla R, Zhang Y, Gu X, Iyer R, Lombardo LJ, Trainor GL, Ruepp S, Lippy J, Blat Y, Sack JS, Khan JA, Stefanski K, Sleczka B, Mathur A, Sun JH, Wong MK, Wu DR, Li P, Gupta A, Arunachalam PN, Pragalathan B, Narayanan S, K C N, Kuppusamy P, Purandare AV. 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. doi: 10.1021/acsmedchemlett.5b00226. PMID: 26288683; PMCID: PMC4538448.
In vivo protocol: 1. Mace TA, Shakya R, Elnaggar O, Wilson K, Komar HM, Yang J, Pitarresi JR, Young GS, Ostrowski MC, Ludwig T, Bekaii-Saab T, Bloomston M, Lesinski GB. 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. doi: 10.18632/oncotarget.6332. PMID: 26575024; PMCID: PMC4792572. 2. Pomicter AD, Eiring AM, Senina AV, Zabriskie MS, Marvin JE, Prchal JT, O'Hare T, Deininger MW. Limited efficacy of BMS-911543 in a murine model of Janus kinase 2 V617F myeloproliferative neoplasm. Exp Hematol. 2015 Jul;43(7):537-45.e1-11. doi: 10.1016/j.exphem.2015.03.006. Epub 2015 Apr 24. PMID: 25912019; PMCID: PMC4487517.

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1: Purandare AV, McDevitt TM, Wan H, You D, Penhallow B, Han X, Vuppugalla R, Zhang Y, Ruepp SU, Trainor GL, Lombardo L, Pedicord D, Gottardis MM, Ross-Macdonald P, de Silva H, Hosbach J, Emanuel SL, Blat Y, Fitzpatrick E, Taylor TL, McIntyre KW, Michaud E, Mulligan C, Lee FY, Woolfson A, Lasho TL, Pardanani A, Tefferi A, Lorenzi MV. Characterization of BMS-911543, a functionally selective small-molecule inhibitor of JAK2. Leukemia. 2012 Feb;26(2):280-8. doi: 10.1038/leu.2011.292. Epub 2011 Oct 21. PubMed PMID: 22015772. 



Additional Information

In vitro activity of BMS-911432: (Source: Leukemia. 2012 Feb;26(2):280-8.)