Description
InformationCOTI-2 COTI-2 is an orally available third generation thiosemicarbazone and activator of mutant forms of the p53 protein, with potential antineoplastic activity.Targetsp53 mutantsIn vitroThe thiosemicarbazone COTI-2 is reported to promote refolding of mutant p53 and restore wild-type-p53 function. It is active against human tumour cell lines of various origins at nanomolar concentrations, induces cell death by apoptosis. COTI-2 is highly efficacious against multiple cancer cell lines from a broad range of human cancers both in vitro and in vivo. COTI-2 does not significantly inhibit over 200 kinases from major kinase pathways involved in cancer that were evaluated in both kinase assays and does not inhibit the ATPase activity of Hsp90, a ubiquitous molecular chaperone that plays an essential role in cell survival and cell cycle control.In vivoCOTI-2 significantly inhibited tumor growth in the HT-29 human colorectal tumor xenografts at a dose of 10 mg/kg. COTI-2 also significantly inhibited tumor growth in the SHP-77 SCLC xenograft model at a dose as low as 3 mg/kg. Its treatment delays U87-MG, MDA-MB-231 and OVCAR-3 xenograft growth. COTI-2 treatment demonstrates a safe toxicity profile in vivo. COTI-2 selectively targets a wide variety of human cancer cell lines, as demonstrated by the in vitro data, while having little deleterious effects on normal cells.Cell Research(from reference)Cell lines：SHP-77 cells Concentrations：100, 250, 1000 nM Incubation Time：48 h