SK-575 is a degradation agent targeting protein-hydrolyzed PARP1 chimera with anticancer and antitumor activity.SK-575 effectively inhibits the growth of cancer cells harboring BRCA1/2 mutations and selectively induces PARP1 degradation in cancer cells.

PARP1 degradation activity:0.509 nM (in SW620 cells), PARP1 degradation activity:1.26 nM (in MDA-MB-436 cells), PARP1 degradation activity:6.72 nM (in Capan-1 cells)

In MDA-MB-436, Capan-1, and SW620 cells, SK-575 (10000, 1000, 300, 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, and 0.01 nM; 24 hours) exhibited significant PARP1 degradation activity, with IC50 values of 1.26, 6.72, and 0.509 nM, respectively[1].

In male BALB/c nude mice bearing xenograft Capan-1 tumors, SK-575 (25 mg/kg, 50 mg/kg; intraperitoneal injection, once daily for 5 consecutive days) inhibited tumor growth. These doses of SK-575 (25 and 50 mg/kg) were well tolerated, with no observed mouse lethality or significant weight loss during the treatment period[1].