PTP Inhibitor XXXI, II-B08-Calbiochem

半岛bd体育手机客户端 说明

一般描述

A cell-permeable indolo-salicylic acid compound that is shown to target SHP2 catalytic domain and inhibit SHP2-catalyzed pNPP hydrolysis (IC₅₀= 5.5 ?M) in a reversible and non-competitive manner (K_i= 5.2 ?M), exhibiting 2.6- to 5.7-fold selectivity over PTP1B, SHP1, FAP1, Lyp, CD45, and LMWPTP (IC₅₀= 14.3, 15.7, 20.3, 25.0, 30.0, and 31.1 ?M, respectively) and >9-fold selectivity over Cdc14A, HePTP, LAR, PTPα, and VHR (IC₅₀>50 ?M). Effectively blocks hyperproliferative activity of human hematopoietic progenitor cells (Effective conc. = 10 ?M) due to SHP2 mutations (D61Y and E76K) or GM-CSF stimulation, as well as c-kit-dependent (via ligand stimulation or D814V mutation), SHP2-mediated myeloid proliferation (Effective conc. = 5 to 75 ?M). Dual PI-3K and SHP2 inhibition by LY294002 (Cat. Nos. 440202 & 440204) and II-B08 (10 mg/kg and 50 mg/kg, respectively; daily i.p.) is shown to greatly prolong the survival rate in a D814V KIT-expressing 32D-based murine MPD (myeloproliferative disease) model (0% survival rate on day 23, 27, 28, respectively, with DMSO, LY294002, II-B08 treatment alone; 20% survival rate on day 65 with combined treatment)in vivo.
A cell-permeable indolo-salicylic acid compound that is shown to target SHP2 catalytic domain and inhibit SHP2-catalyzed pNPP hydrolysis (IC₅₀= 5.5 ?M) in a reversible and non-competitive manner (K_i= 5.2 ?M), exhibiting 2.6- to 5.7-fold selectivity over PTP1B, SHP1, FAP1, Lyp, CD45, and LMWPTP (IC₅₀= 14.3, 15.7, 20.3, 25.0, 30.0, and 31.1 ?M, respectively). Effectively blocks SHP2-mediated human hematopoietic progenitor cell hyperproliferation (10 ?M) due to SHP2 mutations (D61Y and E76K) or GM-CSF stimulation, as well as c-kit-dependent (due to D814V mutation or via ligand stimulation), SHP2-mediated myeloid proliferation (5 to 75 ?M). Dual PI-3K and SHP2 inhibition by LY294002 (Cat. Nos. 440202 & 440204) and II-B08 (10 mg/kg and 50 mg/kg, respectively; daily i.p.) is shown to greatly prolong the survival rate of mice bearing D814V KIT-expressing 32D cellsin vivo.

包装

10 mg in Glass bottle
Packaged under inert gas

生化/生理作用

Secondary Target
Other PTPs
Primary Target
SHP2
Reversible: yes
Target IC₅₀: 5.5, 9.0 and 10.8 µ

警告

Toxicity: Standard Handling (A)

重悬

Following reconstitution, aliquot and freeze (-20°C). Stock solutions are stable for up to 6 months at -20°C.

其他说明

Mali, R.S., et al. 2012.Blood120,2669.
Zhang, X., et al. 2010.J. Med. Chem.53,2482.

法律信息

CALBIOCHEM is a registered trademark of Merck KGaA, Darmstadt, Germany

基本信息

半岛bd体育手机客户端 性质

安全信息