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Current Medicinal Chemistry

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ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

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Review Article

Small Molecules Targeting Mutant P53: A Promising Approach for Cancer Treatment

Author(s): Elizabeth A. Lopes, Sara Gomes, Lucília Saraiva and Maria M.M. Santos*

Volume 26, Issue 41, 2019

Page: [7323 - 7336] Pages: 14

DOI: 10.2174/0929867325666181116124308

Price: $65

Abstract

More than half of all human tumors express mutant forms of p53, with the ovary, lung, pancreas, and colorectal cancers among the tumor types that display the highest prevalence of p53 mutations. In addition, the expression of mutant forms of p53 in tumors is associated with poor prognosis due to increased chemoresistance and invasiveness. Therefore, the pharmacological restoration of wild-type-like activity to mutant p53 arises as a promising therapeutic strategy against cancer. This review is focused on the most relevant mutant p53 small molecule reactivators described to date. Despite some of them have entered into clinical trials, none has reached the clinic, which emphasizes that new pharmacological alternatives, particularly with higher selectivity and lower adverse toxic side effects, are still required.

Keywords: Cancer, chemotherapy, p53 tumor suppressor, reactivators, mutant p53, small molecules.

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