SK-575 is a highly potent and specific proteolysis-targeting chimera (PROTAC) degrader of PARP1, with an IC50 of 2.30 nM. SK-575 potently inhibits the growth of cancer cells bearing BRCA1/2 mutations.In Vitro:SK-575 inhibits cell growth in MDA-MB-436 and Capan-1 cells, with IC50 values of 19 ± 6 nM and 56 ± 12 nM, respectively.
SK-575 (0-1 μM, 24 h) shows good PARP1 degradation activity in cancer cell lines (MDA-MB-436, Capan-1, and SW620 cells).
SK-575 (0-10 μM, 24 h) effectively induces the formation of γH2AX in MDA-MB-436 and Capan-1 cells in a dose dependent manner.
In Vivo:SK-575 (mice bearing BRCA2-mutated Capan-1 xenografts, 25 and 50 mg/kg, IP, once daily for 5 days) significantly inhibits the tumor growth in vivo as a single-agent in HR-deficient xenograft models.
SK-575 (25 mg/kg, IP, once) achieves sufficient exposure in plasma for over 24 h and effectively induces PARP1 degradation in the SW620 xenograft tumor tissue with the effect persisting for >24 h.