您好,欢迎来到化工原料网! [登录] [免费注册]
化工原料网
位置:首页 > 产品库 > AMG 925 HCl
立即咨询
咨询类型:
     
*姓名:
*电话:
*单位:
Email:
*留言内容:
请详细说明您的需求。
*验证码:
 
AMG 925 HCl
本产品不向个人销售,仅用作科学研究,不用于任何人体实验及非科研性质的动物实验。
AMG 925 HCl图片
CAS NO:1401034-19-2
规格:98%
分子量:508.02
包装与价格:
包装价格(元)
200mg电议
500mg电议
5mg电议
10mg电议
50mg电议
100mg电议

产品介绍
AMG 925 HCl 是一种有效的选择性的 FLT3/CDK4 双重抑制剂,IC50 分别为 2±1 nM 和 3±1 nM。
CAS:1401034-19-2
分子式:C26H30ClN7O2
分子量:508.02
纯度:98%
存储:Store at -20°C

Background:

AMG 925 HCl is a potent, selective, and orally available FLT3/CDK4 dual inhibitor with IC50s of 2±1 nM and 3±1 nM, respectively. FLT3|2 nM (IC50)|CDK4|3 nM (IC50)|CDK6|8 nM (IC50)|CDK2|375 nM (IC50)|CDK1|1.9 μM (IC50)


AMG 925 also inhibits CDK6, CDK2, and CDK1 in kinase assays with IC50s of 8±2 nM, 375±150 nM, 1.90±0.51 μM, respectively. A fair overall kinase selectivity of AMG 925 is as determined by KinomScan against a panel of 442 various kinases. Cellular selectivity (on-target vs. off-target activity) of AMG 925 is about 50-fold as evaluated by comparison of its growth-inhibiting activity in RB-positive (RB+) and RB-negative (RB-) non- acute myeloid leukemia (AML) cancer cell lines. AMG 925 potently inhibits growth of AML cell lines MOLM13 (FLT3-ITD; IC50=19 μM) and Mv4-11 (FLT3-ITD; IC50=18 μM)[1].


MOLM13 tumor-bearing mice are dosed twice daily by oral administration 6 hours apart with 12.5, 25, or 37.5 mg/kg AMG 925. Tumors are then harvested 3, 9, 12, and 24 hours after the first dose, and analyzed for levels of P-STAT5 and P-RB. Maximum inhibition of P-STAT5 and P-RB is achieved at 6 and 12 hours respectively at the 37.5 mg/kg dose of AMG 925. Interestingly, a rebound of P-STAT5 at 24 hours is observed, possibly as a result of compensational feedback. The pharmacodynamic responses of P-STAT5 and P-RB inhibition correlated with plasma concentrations of AMG 925. AMG 925 inhibits AML xenograft tumor growth by 96% to 99% without significant body weight loss. The antitumor activity of AMG 925 correlates with the inhibition of STAT5 and retinoblastoma protein (RB) phosphorylation, the pharmacodynamic markers for inhibition of FLT3 and CDK4, respectively. In addition, AMG 925 is also found to inhibit FLT3 mutants (e.g., D835Y) that are resistant to the current FLT3 inhibitors (e.g., AC220 and Sorafenib)[1].


[1]. Keegan K, et al. Preclinical evaluation of AMG 925, a FLT3/CDK4 dual kinase inhibitor for treating acute myeloid leukemia. Mol Cancer Ther. 2014 Apr;13(4):880-9.