MK-0731 是一种选择的、非竞争性变构纺锤体驱动蛋白 (KSP) 抑制剂，IC50为 2.2 nM，pKa为 7.6。MK-0731 对其他驱动蛋白的选择性 >20,000 倍。MK-0731 诱导有丝分裂停滞并诱导肿瘤细胞凋亡。MK-0731 具有显着的抗肿瘤功效。
| 生物活性 | MK-0731 is a selective, non-competitive and allosterickinesinspindle protein (KSP)inhibitor with anIC50of 2.2 nM and apKaof 7.6. MK-0731 is >20,000 fold selectivity against other kinesins. MK-0731 induces mitotic arrest and inducesapoptosisin tumors. MK-0731 provides significant antitumor efficacy[1][2]. |
| IC50& Target[1] | |
体外研究
(In Vitro) | MK-0731 (0.415-300 nM; 48 小时) 诱导 A2780 细胞凋亡，EC50为 2.7 nM[1]。
MK-0731 对结合 hERG 通道的亲和力很小 (IC50=20.5 μM)[1]。
MK-0731 能够在细胞中诱导有丝分裂阻滞，IC50为 19 nM[1]。
Apoptosis Analysis[1] | Cell Line: | A2780 cells | | Concentration: | 0.415-300 nM | | Incubation Time: | 48 h | | Result: | Induced apoptosis with an EC50of 2.7 nM. |
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体内研究
(In Vivo) | MK-0731(40 mg/kg/天; 皮下注射; 持续 11 天) 抑制高度过表达 Pgp 的 KB-v 肿瘤的生长，而紫杉醇 (HY-B0015) 没有作用[1]。
MK-0731 (2.5, 5, 10, 20, 40 mg/kg/天; 微型泵) 在 A2780 异种移植小鼠的肿瘤暴露和有丝分裂停滞方面表现出与剂量成比例的增加[1]。
MK-0731 (1 mg/kg/天; iv) 对于大鼠的 T1/2为 1 小时，CL 为 66 mL/minokg，Vss3 L/kg[1]。
Pharmacokinetic Parameters of MK-0731 in rats[1].
| rat iv (1 mg/kg) | dog iv (0.4 mg/kg) | rhesus iv (0.4 mg/kg) | | T1/2(h) | 1 | 2 | 1 | | CL (mL/min/kg) | 66.7 | 15.1 | 23.1 | | Vss(L/kg) | 3.0 | 1.6 | 2.3 |
| Animal Model: | Mice for the dual flank xenograft KB-3-1 and KB-v-1 cells[1] | | Dosage: | 40 mpk | | Administration: | SC; qd×1; for 11 days | | Result: | Inhibited the growth of KB-v tumors that highly overexpress Pgp, whereas Paclitaxel (20 mpk; qd×5) had no effect. |
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| 运输条件 | Room temperature in continental US; may vary elsewhere. |
| 储存方式 | Please store the product under the recommended conditions in the Certificate of Analysis. |
| 溶解性数据 | In Vivo: 1. formulated as a solution in acidified saline at pH 4.0, 100 μL
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