SK-575 (C007B-417784)

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 mutationsIn VitroSK-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 VivoSK-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) 3.08Form:SolidIC50& Target:PARP1 2.30 nM (IC 50 ).

Specifications and Purity: ≥99%

Molecular Formula: C47H53FN8O8

Molecular Weight: 876.97