MPK-09, a small molecule inspired from bioactive styryllactone restores the wild-type function of mutant p53

Metri, Prashant K and Naz, Sarwat and Kondaiah, Paturu and Prasad, Kavirayani R (2013) MPK-09, a small molecule inspired from bioactive styryllactone restores the wild-type function of mutant p53. In: ACS Chemical Biology, 8 (7). pp. 1429-1434.

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Abstract

In the search for more efficacious and less toxic cancer drugs, the tumor suppressor p53 protein has long been a desirable therapeutic target. In the recent past, few independent studies have demonstrated that the antitumor activity of wild-type p53 can be restored in cancer cells harboring mutant form of p53 using small molecule activators. In this study, we describe a novel small molecule MPK-09, which is selective and highly potent against allele specific p53 mutations mainly, R175H, R249S, R273H, R273C, and E285K. Except E285K, all other mutations tested are among the six ``hot spot'' p53 mutations reported in majority of human cancer. Furthermore, our study conclusively demonstrates that the apoptotic activity of the small molecule MPK-09 against cancer cells harboring R273C and E285K mutations is due to restoration of the wild-type conformation to the corresponding mutant form of p53.

Item Type:	Journal Article
Publication:	ACS Chemical Biology
Publisher:	American Chemical Society
Additional Information:	Copyright of this article belongs to American Chemical Society.
Department/Centre:	Division of Biological Sciences > Molecular Reproduction, Development & Genetics Division of Chemical Sciences > Organic Chemistry
Date Deposited:	01 Oct 2013 11:30
Last Modified:	01 Oct 2013 11:30
URI:	http://eprints.iisc.ac.in/id/eprint/47443

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