title: MPK-09, a small molecule inspired from bioactive styryllactone restores the wild-type function of mutant p53.
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.
authors.affiliation: Department of Organic Chemistry and ‡Department of Molecular Reproduction Development and Genetics, Indian Institute of Science , Bangalore 560012, India.
authors.forename: Prashant K
authors.initials: PK
authors.lastname: Metri
authors.forename: Sarwat
authors.initials: S
authors.lastname: Naz
authors.forename: Paturu
authors.initials: P
authors.lastname: Kondaiah
authors.forename: Kavirayani R
authors.initials: KR
authors.lastname: Prasad
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D002087:Butyrates / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004988:Ethers, Cyclic / Q000737:chemistry* / Q000494:pharmacology*; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D017353:Gene Deletion; D006801:Humans; D020128:Inhibitory Concentration 50; D007783:Lactones / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009154:Mutation; D013343:Styrenes / Q000737:chemistry / Q000494:pharmacology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D002087:Butyrates; D004988:Ethers, Cyclic; D007783:Lactones; C000592893:MPK-09; D013343:Styrenes; D016159:Tumor Suppressor Protein p53