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SHP099
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。
SHP099图片
CAS NO:1801747-42-1
规格:98%
分子量:352.3
包装与价格:
包装价格(元)
500ug电议
1mg电议
5mg电议
10mg电议

产品介绍
SHP099 is an orally bioavailable inhibitor of SHP2, a non-receptor protein tyrosine phosphatase (IC50 = 71 nM).
CAS:1801747-42-1
分子式:C16H19Cl2N5
分子量:352.3
纯度:98%
存储:Store at -20°C

Background:

SHP099 is a potent, selective, orally available SHP2 inhibitor with an IC50 of 70 nM.


The X-ray co-crystal for SHP099 with SHP2 reveals a new interaction with the basic amine and the Phe113 backbone carbonyl. SHP099 shows inhibition of cell proliferation (KYSE-520 model) with an IC50 of 1.4 μM. SHP099 shows high solubility and high permeability with no apparent efflux in Caco-2 cells[1]. SHP099 concurrently binds to the interface of the N-terminal SH2, C-terminal SH2, and protein tyrosine phosphatase domains, thus inhibiting SHP2 activity through an allosteric mechanism. SHP099 suppresses RAS–ERK signalling to inhibit the proliferation of receptor-tyrosine-kinase-driven human cancer cells[2].


After a single doses of 30 and 100 mg/kg (red and blue lines, respectively), dose-dependent exposure and modulation of the pharmacodynamic marker p-ERK is observed in the xenografts. A daily oral dose of 10 or 30 mg/kg yield 19% and 61% tumor growth inhibition, respectively. Tumor stasis is achieved at 100 mg/kg[1].


参考文献:
[1]. Garcia Fortanet J, et al. Allosteric Inhibition of SHP2: Identification of a Potent, Selective, and Orally Efficacious Phosphatase Inhibitor. J Med Chem. 2016 Sep 8;59(17):7773-82.
[2]. Chen YN, et al. Allosteric inhibition of SHP2 phosphatase inhibits cancers driven by receptor tyrosine kinases. Nature. 2016 Jul 7;535(7610):148-52.