UCI-LC0019

UCI-LC0019 is a mutant p53 reactivator. UCI-LC0019 binds to mutant p53, induces wild-type-like conformational change, restores sequence-specific DNA binding activity, activates p53-dependent transcription programs, and does not act via thiol reactivity or glutathione depletion. UCI-LC0019 inhibits proliferation and induces apoptosis in cancer cells harboring mutant p53, with no significant effect on p53 null or wild-type p53 tumors cells. UCI-LC0019 exhibits anti-tumor activity in xenograft mouse models carrying p53 R175H mutant tumors. UCI-LC0019 can be used for the research of cancer, such as ovarian cancer ^[1].

In Vivo, UCI-LC0019 (10 mg/kg; i.p.; daily for 10 days) inhibits tumor growth in mice with p53R175H-expressing TOV112D Xenografts^[1].

In Vitro, UCI-LC0019 potently inhibits proliferation of p53G245S-expressing Saos-2 cells (IC₅₀ = 16.5 μM) and p53R175H-expressing TOV112D cells (IC₅₀ = 15.2 μM) with reduced activity against p53null Saos-2 cells (IC₅₀ = 24.1 μM)^[1]. UCI-LC0019 (0-30 μM; 3-72 h) rapidly reduces proliferation and induces apoptosis in p53R175H-expressing TOV112D cells^[1]. UCI-LC0019 (25-30 μM; 3 days) inhibits proliferation of p53R175H-expressing TOV112D cells via a mechanism independent of thiol reactivity, as co-treatment with 5 mM NAC does not reverse its antiproliferative effects^[1].

References:
[1]. Durairaj G, et al. Discovery of compounds that reactivate p53 mutants in vitro and in vivo. Cell Chem Biol. 2022;29(9):1381-1395.e13.