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BMS-911543

现货
Catalog No.
A4152
JAK2抑制剂
组合的产品项目
规格价格库存 数量
5mg
¥ 1,310.00
Ship with 10-15 days
10mg
¥ 2,310.00
Ship with 10-15 days
25mg
¥ 3,560.00
Ship with 10-15 days
50mg
¥ 7,600.00
Ship with 10-15 days

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Background

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

StorageStore at -20°C
M.Wt432.52
Cas No.1271022-90-2
FormulaC23H28N8O
Solubility≥43.3 mg/mL in DMSO with gentle warming, ≥9.8 mg/mL in EtOH with ultrasonic and warming, <2.48 mg/mL in H2O
SDFDownload SDF
Canonical SMILESCCN1C(=CC2=C3C(=C(N=C21)NC4=NN(C(=C4)C)C)N=CN3C)C(=O)N(C5CC5)C6CC6
运输条件试用装:蓝冰运输。 其他可选规格:常温运输或根据您的要求用蓝冰运输。
一般建议为了使其更好的溶解,请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异,仅做参考。若实验所需浓度过大至产品溶解极限,请添加助溶剂助溶或自行调整浓度。

试验操作

细胞实验[1, 2]:

细胞系

表达JAK2V617F的SET2和Ba/F3细胞;人血小板;从表达JAK2V617F、JAK2EXON12或MPLW515L突变的MPN患者分离的原代造血祖细胞

溶解方法

该化合物溶于DMSO。为了获得更高的浓度,可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。

反应条件

0-10 μM; 6, 16 or 24 h

应用

在用于表达JAK2V617F的SET2和Ba/F3细胞中,BMS-911543显示剂量依赖性的抗增殖作用,IC50值分别为60和70nM。在人血小板中,BMS-911543以剂量依赖性方式抑制TPO刺激的pSTAT5。在从表达JAK2V617F,JAK2EXON12或MPLW515L突变的MPN患者分离的原发性造血祖细胞中,BMS-911543抑制EPO介导的爆裂形成单位红细胞(BFU-E)集落生长,IC50范围为<0.150~0.9μM。

动物实验[1]:

动物模型

BALB/c小鼠; SET2细胞异种移植的无胸腺小鼠

剂量

5, 10 和30mg/kg, 18h; 1, 2, 5和10 mg/kg, 口服

应用

在用BMS-911543处理的BALB / c小鼠中,分离血小板并用TPO处理以诱导pSTAT5。在30mg / kg时,BMS-911543在所有时间点(给药后1-18小时)完全抑制pSTAT5的诱导。BMS-911543在10mg / kg时诱导约75%的pSTAT5减少至18小时。5mg / kg BMS-911543显示TPO刺激的pSTAT5减少约50%至约8h。在SET2细胞异种移植的无胸腺小鼠中,10mg / kg BMS-911543在给药后7小时显示出90-100%的pSTAT5抑制。

注意事项

请测试所有化合物在室内的溶解度,实际溶解度和理论值可能略有不同,这是由实验系统的误差引起的,属于正常现象。

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.

生物活性

描述 BMS-911543是一种选择性的Janus酪氨酸激酶2(JAK2)小分子抑制剂,IC50值为1 nM。
靶点 JAK2          
IC50 1 nM          

质量控制

化学结构

BMS-911543