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 > Danusertib(PHA-739358)
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:
 
Danusertib(PHA-739358)
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。
Danusertib(PHA-739358)图片
包装与价格:
包装价格(元)
10mM (in 1mL DMSO)电议
5mg电议
10mg电议
50mg电议

产品介绍
Danusertib (PHA-739358) 是一种吡咯并吡唑和极光激酶抑制剂,对极光 A、B 和 C 的 IC50 分别为 13、79 和 61 nM。

Biochemical kinase assays

The Km values for ATP and the specific substrate were initially determined, and each assay was then run at optimized ATP (2Km) and substrate (5Km) concentrations. This setting enabled direct comparison of IC50 values of Danusertib across the applied kinase selectivity screening panel for the evaluation of the selectivity profile.

Cell lines

CD34+ cells

Preparation method

The solubility of this compound in DMSO is >10 mM. 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.

Reaction Conditions

5 μM; 5 days

Applications

In CD34+ cells from an IM-resistant CML patient, Danusertib induced apoptosis and reduced phosphorylation of P-CrkL.

Animal models

Female SCID mice s.c. injected with K562 cells

Dosage form

15 mg/kg; i.p.; b.i.d., for 10 days

Applications

Danusertib significantly inhibited K562 cell proliferation and virtually suppressed tumor growth.

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.

产品描述

Danusertib (previously known as PHA-739358), a 3-aminopyrazole derivative identified during the development of the pyrrolopyrazole sub-series, is a potent small-molecule inhibitor of aurora kinases family members with a dominant inhibition for aurora B kinase (ABK). This pan-aurora kinases inhibitor is also able to inhibit several tyrosine kinases, including T315I mutant, Ret, Trk-A and fibroblast growth factor receptor-1 (FGFR-1), which are involved in multiple malignancies, such as chronic myelogenous leukemia (CML), acute lymphoblastic leukemia (ALL), thyroid prostate and breast carcinoma. Thus, in many previous studies, danusertib exhibits remarkable antitumor activity in a number of different xengorafts, spontaneous, and transgenic animal tumor models with a favorable pharmacokinetic and safety profile.

Reference

[1].Carpinelli P, Ceruti R, Giorgini ML, Cappella P, Gianellini L, Croci V, Degrassi A, Texido G, Rocchetti M, Vianello P, Rusconi L, Storici P, Zugnoni P, Arrigoni C, Soncini C, Alli C, Patton V, Marsiglio A, Ballinari D, Pesenti E, Fancelli D, Moll J. PHA-739358, a potent inhibitor of aurora kinases with a selecyive target inhibiton profile relevant to cancer. Mol Cancer Ther 2007; 6(12 Pt 1): 3158-3168