KRIBB3 is an Hsp27 and microtubule inhibitor that inhibits migration and invasion of MDA-MB-231 cells in vitro in an Hsp27-dependent manner.[1] [2] It inhibits protein kinase C (PKC) phosphorylation of Hsp27 but not phospholipase Cβ3, indicating KRIBB3 interaction with Hsp27 is preventing its phosphorylation. KRIBB3 (1-100 μM) inhibits growth of HCT116, HCT15, and MDA-MB-231 cells in an Hsp27-independent and concentration-dependent manner. It induces HCT116 cell cycle arrest in the G2/M phase via formation of the Mad2/p55CDC inhibitory complex and Bax activation of apoptosis.[2] KRIBB3 also inhibits microtubule polymerization in HCT116 cells. In vivo, KRIBB3 (50-100 mg/kg) reduces tumor volume in an HCT116 mouse xenograft model.
Reference:
[1]. Shin, K.D., Lee, M.-Y., Shin, D.-S., et al. Blocking tumor cell migration and invasion with biphenyl isoxazole derivative KRIBB3, a synthetic molecule that inhibits Hsp27 phosphorylation. J. Biol. Chem. 280(50), 41439-41448 (2005).
[2]. Shin, K.D., Yoon, Y.J., Kang, Y.-R., et al. KRIBB3, a novel microtubule inhibitor, induces mitotic arrest and apoptosis in human cancer cells. Biochem. Pharmacol. 75(2), 383-394 (2008).