The invention herein disclosed relates to tryptophanol oxazolo derivatives, the compounds SLMP53-1 and SLMP53-2, as new small-molecule activators of wild-type and mutant p53, with a potential use as an anticancer therapeutic.
The tumor suppressor p53 is an attractive anticancer therapeutic target because it can be functionally activated to eradicate tumors. As such, several compounds targeting the p53 pathway have emerged. In spite of this, more potent and selective pharmacological alternatives to the activation of p53 function for neoplastic cells are still largely required, specially avoiding deleterious adverse effects associated with many of the current cancer therapies. The possible identification of small-molecules that restore wild-type p53 function to a broad range of p53 mutants paved the way to a new class of anticancer agents more efficient in personalized therapy of cancer patients, and with low adverse effects on normal cells.
SLMP53-1 and SLMP53-2 have p53-dependent anti-proliferative activity in wild-type and mutant p53-expressing human cancer cells. SLMP53-1 and SLMP53-2 are non-genotoxic and have low cytotoxicity against normal cells. Importantly, both compounds display antitumor activity, with no apparent toxic side effects, in xenograft mouse models.
The compounds can be used as probes in the wild-type and mutant p53-signalling pathway research field and as anticancer therapeutics after further development.
A proteção dos direitos de propriedade industrial é cofinanciada por: