靶点：Bcr-Abl 通路：Protein Tyrosine Kinase/RTK 背景说明：GNF-2是非ATP竞争性的Bcr-Abl选择性抑制剂。 生物活性：GNF-2 is a highly selective， allosteric， non-ATP competitive inhibitor of Bcr-Abl. GNF-2 inhibits Ba/F3.p210 proliferation with an IC50 of 138 nM [1]. IC50：Bcr-Abl In Vitro：GNF-2 selectively inhibits Bcr-abl-dependent cell proliferation. GNF-2 (0.005-10 μM; 48 hours) specifically inhibits the proliferation of the Bcr-abl-expressing cells with an IC50 of 138 nM and not show any cytotoxic effects on the nontransformed cells at concentrations of up to 10 μM. GNF-2 (0.005-10 μM; 48 hours) causes a dose-dependent growth inhibition of the Bcr-abl-positive cell lines with IC50 values of 273 nM (K562) and 268 nM (SUP-B15). GNF-2 (0.005-10 μM; 48 hours) inhibits E255V and Y253H mutant Bcr-abl cell growth (IC50 values of 268 and 194 nM， respectively)[1].GNF-2 (1-10 μM; 48 hours) induces apoptosis of Bcr-abl-transformed cells[1].GNF-2 (0.1-10 μM; 90 minutes) inhibits the cellular tyrosine phosphorylation of Bcr-abl in a dose-dependent manner with an IC50 of 267 nM[1]. In Vivo：GNF-2 (10 mg/kg; i.p. for 8 days) protects LPS (5 mg/kg) induced bone erosion in mice. GNF-2 protects the LPS induced bone loss and abrogates the LPS-induced decreases of bone volume/tissue volume (BV/TV) of LPS-treated mice[2].GNF-2 prevents the LPS-induced increases of N.Oc/B.Pm， the percentage of Oc.S/BS， and the percentage of ES/BS[2]. 数据来源文献：[1]. Adrián FJ， et al. Allosteric inhibitors of Bcr-abl-dependent cell proliferation. Nat Chem Biol. 2006 Feb;2(2):95-102. [2]. Kim HJ， et al. The tyrosine kinase inhibitor GNF-2 suppresses osteoclast formation and activity. J Leukoc Biol. 2013 Oct 15.
扫一扫关注我们
