Home>>Signaling Pathways>> JAK/STAT Signaling>> JAK>>BMS-911543

BMS-911543 Sale

目录号 : GC12454

A potent, selective JAK2 inhibitor

BMS-911543 Chemical Structure

Cas No.:1271022-90-2

规格 价格 库存 购买数量
10mM (in 1mL DMSO)
¥832.00
现货
2mg
¥665.00
现货
5mg
¥875.00
现货
10mg
¥1,540.00
现货
50mg
¥5,600.00
现货
100mg
¥8,400.00
现货

电话:400-920-5774 Email: sales@glpbio.cn

Customer Reviews

Based on customer reviews.

Sample solution is provided at 25 µL, 10mM.

产品文档

Quality Control & SDS

View current batch:

实验参考方法

Cell experiment [1, 2]:

Cell lines

SET2 and Ba/F3 cells engineered to express JAK2V617F; human platelets; primary hematopoetic progenitor cells isolated from MPN patients that expressed JAK2V617F, JAK2EXON12 or MPLW515L mutations

Preparation method

This compound is soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months.

Reacting condition

0-10 μM; 6, 16 or 24 h

Applications

In SET2 and Ba/F3 cells engineered to express JAK2V617F, BMS-911543 exhibited a dose-dependent anti-proliferative effect with IC50 values of 60 and 70 nM, respectively. In human platelets, BMS-911543 inhibited TPO-stimulated pSTAT5 in a dose-dependent manner. In primary hematopoetic progenitor cells isolated from MPN patients that expressed JAK2V617F, JAK2EXON12 or MPLW515L mutations, BMS-911543 inhibited EPO-mediated burst forming unit-erythroid (BFU-E) colony growth with IC50 ranging from <0.150 to ~0.9 μM.

Animal experiment [1]:

Animal models

BALB/c mice; athymic mice xenografted with SET2 cells

Dosage form

5, 10 and 30mg/kg, 18h; 1, 2, 5 and 10 mg/kg, orally administered

Application

In BALB/c mice treated with BMS-911543, platelets were isolated and treated with TPO to induce the pSTAT5. At 30mg/kg, BMS-911543 fully suppressed pSTAT5 induction at all time points (1–18 h post dose). BMS-911543 induced ~75% reduction up to 18 h at 10mg/kg. 5mg/kg BMS-911543 revealed a roughly 50% reduction in TPO-stimulated pSTAT5 by ~8 h. In athymic mice xenografted with SET2 cells, 10mg/kg BMS-911543 showed 90–100% inhibition of pSTAT5 up to 7 h post dose.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

References:

[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.

[2]. Wan H1, Schroeder GM1, Hart AC1, 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.

产品描述

BMS-911543 is a selective small-molecule inhibitor of JAK2 with IC50 value of 1.1nM [1].

BMS-911543 is a reversible pyrrolopyridine ATP-competitive JAK2 inhibitor with a high selectivity. In the in vitro assay using human recombinant JAK enzyme, BMS-911543 displays an IC50 value of 1.1nM against JAK2 and the Ki value is 0.48nM. The inhibition activity and affinity against JAK2 are both much higher than those against JAK1 and JAK3. Besides that, BMS-911543 also has efficacy against other kinases, such as Lyn and the c-FMS receptor tyrosine kinase. In JAK-dependent cells such as SET2 or Ba/F3, the treatment of BMS-911543 causes an anti-proliferative effect with IC50 values of 60 and 70nM, respectively. The cell lines depending on other JAK family members do not show significant anti-proliferative response to BMS-911543. The colony growth assays prove that BMS-911543 can suppress the growth of MPN patient-derived cells and is more potent in the JAK2V617F pathway compared with the JAK2WT pathway. BMS-911543 is also found to be potent in vivo in both the JAK2WT pathway and the JAK2V617F pathway through suppressing pSTAT5 induction [1].

References:
[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.

Chemical Properties

Cas No. 1271022-90-2 SDF
Canonical SMILES CCN1C(=CC2=C3C(=C(N=C21)NC4=NN(C(=C4)C)C)N=CN3C)C(=O)N(C5CC5)C6CC6
分子式 C23H28N8O 分子量 432.52
溶解度 ≥ 43.3 mg/mL in DMSO with gentle warming, ≥ 9.8 mg/mL in EtOH with ultrasonic and warming 储存条件 Store at -20°C
General tips 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液;一旦配成溶液,请分装保存,避免反复冻融造成的产品失效。
储备液的保存方式和期限:-80°C 储存时,请在 6 个月内使用,-20°C 储存时,请在 1 个月内使用。
为了提高溶解度,请将管子加热至37℃,然后在超声波浴中震荡一段时间。
Shipping Condition 评估样品解决方案:配备蓝冰进行发货。所有其他可用尺寸:配备RT,或根据请求配备蓝冰。

溶解性数据

制备储备液
1 mg 5 mg 10 mg
1 mM 2.312 mL 11.5602 mL 23.1203 mL
5 mM 0.4624 mL 2.312 mL 4.6241 mL
10 mM 0.2312 mL 1.156 mL 2.312 mL
  • 摩尔浓度计算器

  • 稀释计算器

  • 分子量计算器

质量
=
浓度
x
体积
x
分子量
 
 
 
*在配置溶液时,请务必参考产品标签上、MSDS / COA(可在Glpbio的产品页面获得)批次特异的分子量使用本工具。

计算

动物体内配方计算器 (澄清溶液)

第一步:请输入基本实验信息(考虑到实验过程中的损耗,建议多配一只动物的药量)
给药剂量 mg/kg 动物平均体重 g 每只动物给药体积 ul 动物数量
第二步:请输入动物体内配方组成(配方适用于不溶于水的药物;不同批次药物配方比例不同,请联系GLPBIO为您提供正确的澄清溶液配方)
% DMSO % % Tween 80 % saline
计算重置