SK-575 是一种高效、特异的蛋白水解靶向嵌合体 (PROTAC) 的PARP1降解剂，其IC50为2.30 nM。SK-575 能有效抑制携带 BRCA1/2 突变的癌细胞的生长。
| 生物活性 | SK-575 is a highly potent and specific proteolysis-targeting chimera (PROTAC) degrader ofPARP1, with anIC50of 2.30 nM. SK-575 potently inhibits the growth ofcancercells bearing BRCA1/2 mutations[1]. |
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体外研究
(In Vitro) | SK-575 抑制 MDA-MB-436 和 Capan-1 细胞生长，IC50值分别为 19±6 nM 和 56±12 nM[1]。
SK-575 (0-1 μM，24 h) 在癌细胞系 (MDA-MB-436、Capan-1 和 SW620 细胞)中显示出良好的 PARP1 降解活性[1]。
SK-575 (0-10 μM, 24 h) 诱导 MDA-MB-436 和 Capan-1 细胞生成 γH2AX，呈剂量依赖性[1]。
Western Blot AnalysisM[1] | Cell 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), withIC50values 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. |
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体内研究
(In Vivo) | SK-575 (25 和 50 mg/kg，腹腔注射，每天一次，持续 5 天) 在 HR 缺陷异种移植模型中作为单一药物显著抑制体内肿瘤生长[1]。
SK-575 (25 mg/kg，腹腔注射，单次)在血浆中充分暴露超过 24 小时，并有效诱导 SW620 异种移植肿瘤组织中的 PARP1 降解，效果持续 >24 小时[1]。
| Animal Model: | Male BALB/c nude mice (bearing xenograft Capan-1 tumors)[1] | | 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)[1] | | Dosage: | 25 mg/kg | | Administration: | Intraperitoneally, a single dose (Pharmacokinetic Analysis) | | Result: | Pharmacokinetic Parameters of SK-575 in female ICR mice[1].
| Parameters | mean | | Tmax(h) | 0.25 | | Cmax(ng/mL) | 1843 | | AUCall(ng/mL*h) | 5316 | | AUCinf(ng/mL*h) | 5363 | | t1/2(ng/mL) | 3.08 |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | -20°C, sealed storage, away from moisture and light *In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture and light) |
| 溶解性数据 | In Vitro: DMSO : 100 mg/mL(114.03 mM;Need ultrasonic) 配制储备液 | 1 mM | 1.1403 mL | 5.7014 mL | 11.4029 mL | | 5 mM | 0.2281 mL | 1.1403 mL | 2.2806 mL | | 10 mM | 0.1140 mL | 0.5701 mL | 1.1403 mL |
*请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。
储备液的保存方式和期限：-80℃, 6 months; -20℃, 1 month (sealed storage, away from moisture and light)。-80℃ 储存时，请在 6 个月内使用，-20℃ 储存时，请在 1 个月内使用。 |
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