STAT3/STAT5 Dual Inhibitor, SH-4-54-Calbiochem

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一般描述

A cell-permeable, salicyclic-to-benzoic acid-substituted BP-1-102 (Cat. no. 573132) analog that targets STAT3 and STAT5 with comparable affinity (k_off/k_on=K_D= 300 and 464 nM, respectively) and is 4-fold more potent in competing against phosphopeptide for binding to SH2 domain of STAT3 over STAT1 (K_i= 23.5 and 92.3 ?M, respectively; [phosphopeptide] = 10 nM), exhibiting little potency against the kinase activity of upstream kinases (Akt1, Erk1, JAK1/2, c-Src) or the activation of 21 GPCRs, and displaying much reduced or no affinity toward other kinases in a 101-panel screen. Selectively inhibits cellular STAT3 Y705, but not S727, phosphorylation (0.5 to 5 ?M) and is a more potent anticancer agent than BP-1-102 against gliobalstoma (GMB) patients-derived brain tumor stem cell (BTSC) cultures (IC₅₀from 42 to 530 nM). Reported to penetrate blood-brain-barrier in mice (Conc in brain = 313 nM 30 min post 10 mg/kg i.p. dosing) and effectively inhibit BT73 glioma proliferation in xenografted murine brain via apoptosis induction (10 doses: 10 mg/kg i.p., 4 d on/ 3 d off)in vivo.
A cell-permeable BP-1-102 (Cat. no. 573132) analog that targets STAT3 and STAT5 with comparable affinity and is 4-fold more potent in competing against phosphopeptide for binding SH2 domain of STAT3 over STAT1, exhibiting little potency against upstream kinases or the activation of 21 GPCRs, and displaying much reduced or no affinity toward other kinases in a 101-panel screen. Selectively inhibits cellular STAT3 Y705, but not S727, phosphorylation (0.5 to 5 ?M) and is a more potent anticancer agent than BP-1-102 against gliobalstoma (GMB) patients-derived brain tumor stem cell (BTSC) in cultures (IC₅₀from 42 to 530 nM). Reported to penetrate blood-brain-barrier in mice and effectively inhibit BT73 glioma proliferation in xenografted murine brain (10 mg/kg/d via i.p.; 4 d on/ 3 d off)in vivo.

生化/生理作用

Cell permeable: yes
Secondary Target
STAT5
Reversible: yes

包装

Packaged under inert gas

警告

Toxicity: Standard Handling (A)

其他说明

Haftchenary, S., et al. 2013.ACS Med. Chem. Lett.4,In press.

法律信息

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

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