Journal Article

Mutant p53 targeting by the low molecular weight compound STIMA-1

Bergman, Jan, Rökaeus, Nina, Wiman, Klas G., Lambert, Jeremy M.R., Shen, Jinfeng, Bykov, Vladimir J.N., Hainaut, Pierre, Zache, Nicole

2008

Overview

Reactivation of mutant p53 in human tumor cells should induce cell death by apoptosis and thus eliminate the tumor. Several small molecules that reactivate mutant p53 have been identified. Here we show that STIMA-1, a low molecular weight compound with some structural similarities to the previously identified molecule CP-31398, can stimulate mutant p53 DNA binding in vitro and induce expression of p53 target proteins and trigger apoptosis in mutant p53-expressing human tumor cells. Human diploid fibroblasts are significantly more resistant to STIMA-1 than mutant or wild type p53-carrying tumor cells. STIMA-1 may provide new insights into possible mechanisms of mutant p53 reactivation and thus facilitate the development of novel anticancer drugs that target mutant p53-carrying tumors.

• Publisher: Elsevier B.V,John Wiley & Sons, Inc,John Wiley and Sons Inc
• Subject: Antineoplastic Agents - pharmacology / Antineoplastic drugs / Antitumor agents / Apoptosis / Binding sites / Cancer therapies / Cancer therapy / Cell cycle / Cell death / Cell growth / CP-31398 / DNA - metabolism / Drug Delivery Systems - methods / Drug development / Fibroblasts / Humans / Laboratories / Molecular Weight / Mutant p53 reactivation / Mutant Proteins - drug effects / Mutation / Neoplasms - drug therapy / Neoplasms - pathology / p53 Protein / Peptides / Proteins / Quinazolinones - pharmacology / STIMA-1 / Tumor cells / Tumor Cells, Cultured / Tumor Suppressor Protein p53 - drug effects / Tumor Suppressor Protein p53 - genetics / Tumor Suppressor Protein p53 - metabolism / Tumors / Vinyl Compounds - pharmacology