SK-575

SK-575 is a highly potent and specific proteolysis-targeting chimera ( PROTAC ) degrader of PARP1 , with an IC 50 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 IC 50 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. MCE has not independently confirmed the accuracy of these methods. They are for reference only. Western Blot AnalysisMCell Line: MDA-MB-436, Capan-1, and SW620 cells Concentration: 10000, 1000, 300, 100, 30, 10, 3, 1, 0.3, 0.1, 0.03, and 0.01 nM Incubation Time: 24 h Result: Showed good PARP1 degradation activity in these cancer cell lines (MDA-MB-436, Capan-1, and SW620 cells), with IC 50 values of 1.26, 6.72 and 0.509 nM, respectively. Effectively induced 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 . MCE has not independently confirmed the accuracy of these methods. They are for reference only. Animal Model: Male BALB/c nude mice (bearing xenograft Capan-1 tumors) Dosage: 25 mg/kg, 50 mg/kg Administration: IP, once daily for 5 consecutive days Result: Inhibited tumor growth. SK-575 at these doses (25 and 50 mg/kg) were well tolerated, with no mice lethality or significant weight loss observed during the treatment time. Animal Model: Female ICR mice (20-23 g, 6-7 week-old, n=3 per group) Dosage: 25 mg/kg Administration: Intraperitoneally, a single dose (Pharmacokinetic Analysis) Result: Pharmacokinetic Parameters of SK-575 in female ICR mice . Parameters mean T max (h) 0.25 C max (ng/mL) 1843 AUC all (ng/mL∗h) 5316 AUC inf (ng/mL∗h) 5363 t 1/2 (ng/mL) 3.08 Form:Solid IC50& Target:PARP1 2.30 nM (IC 50 )

No numbering system information yet

No physical and chemical property information yet

No safety information yet

No production method and use information yet

No upstream information yet

No downstream information yet

No related product information yet