Journal
CURRENT MEDICINAL CHEMISTRY
Volume 26, Issue 41, Pages 7323-7336Publisher
BENTHAM SCIENCE PUBL LTD
DOI: 10.2174/0929867325666181116124308
Keywords
Cancer; chemotherapy; p53 tumor suppressor; reactivators; mutant p53; small molecules
Funding
- FCT (Fundacao para a Ciencia e a Tecnologia, Portugal) [PTDC/QUI-QOR/29664/2017, PTDC/DTPFTO/1981/2014-POCI-01-0145-FEDER-016581, UID/QUI/50006/2019, CEECIND/01772/2017, SFRH/BD/96189/2013, SFRH/BD/137544/2018, UID/DTP/04138/2019]
- Fundação para a Ciência e a Tecnologia [SFRH/BD/137544/2018, PTDC/QUI-QOR/29664/2017, SFRH/BD/96189/2013] Funding Source: FCT
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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.
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