The protein p53 is recognized as one of the most important guardians in the body that prevents tumor development. Since its discovery, the roles of p53 have been the focus of research geared toward understanding the mechanisms of uncontrolled cell growth or cancer. Specifically, when healthy cells are damaged, p53 levels increase, followed by inhibition of cell growth or programmed cell death. This regulation of damaged cells is initiated by a p53-DNA binding event. Mutated forms of p53 that lose the ability to bind DNA can not arrest cell growth, and the proliferation of damaged cells results. Mutant forms of p53 are present in approximately 50% of all human cancers. If mutant p53 can be induced to readopt the active form of wild-type p53, tumor suppressor function can be restored. Molecules that reactivate mutant p53 could selectively target tumor cells due to the accumulation of mutated p53 in these cells. In our research, we are developing a unique class of molecules to reactivate mutant p53 associated with cancer. We have developed a synthetically accessible class of molecules that can be easily modified to examine structural activity relationships, mechanism of biological activity, or optimize for anticancer activity, and we are currently examining the activity of these molecules in a variety of cancer cell lines.
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| Myers, Michael C; Wang, Jinling; Iera, Jaclyn A et al. (2005) A new family of small molecules to probe the reactivation of mutant p53. J Am Chem Soc 127:6152-3 |
