14-3-3 Antagonist II, BV02 - Calbiochem

A cell-permeable, non-peptidyl pyrazolylcarbamoyl compound that targets the amphipathic client protein-binding groove of 14-3-3 and effectively competes against cellular pro-apoptotic c-Abl and cell cycle inhibitor protein p27^Kip1 (CDK inhibitor 1B) for 14-3-3ς interaction, leading to c-Abl mitochondrial membrane relocation, c-Abl and p27^Kip1 nuclear translocation, sub-G1 arrest, enhanced c-Abl cleavage, caspase-9 and -8 activation (24 h 5 µM treatment), and eventual apoptotic cell death in pro-B murine Ba/F3 lines expressing wt, E255K, or T315I Bcr-Abl (LD₅₀ = 0.41, 1.30, 1.47 µM, respectively;). Also demonstrated to exhibit antiproliferative activity against the survival of three primary IM- (Imatinib mesylate; STI571) resistant CD34+ cultures (LD₅₀ = 0.5, 0.7, and 2.5 µM) from CML (chronic myeloid leukemia) patients with T315I Bcr-Abl mutation.

Packaged under inert gas

Mancini, M., et al. 2011. J. Pharmacol. Exp. Ther.336, 596.

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

Toxicity: Regulatory Review (Z)