MK-0731

MK-0731 is a selective, non-competitive and allosteric kinesin spindle protein (KSP) inhibitor with an IC₅₀ of 2.2 nM and a pK_a of 7.6. MK-0731 is >20,000 fold selectivity against other kinesins. MK-0731 induces mitotic arrest and induces apoptosis in tumors. MK-0731 provides significant antitumor efficacy^[1][2]. In Vitro: MK-0731 (0.415-300 nM; 48 h) induces apoptosis in A2780 cells with an EC₅₀ of 2.7 nM^[1].
MK-0731 displays little affinity for binding to the hERG channel (IC₅₀=20.5 μM)^[1].
MK-0731 has the ability to induce a mitotic block with an IC₅₀ of 19 nM in cells^[1].
In Vivo: MK-0731 (40 mg/kg/day; sc; for 11 days) inhibits the growth of KB-v tumors that highly overexpress Pgp, whereas Paclitaxel (HY-B0015) has no effect^[1].
MK-0731 (2.5, 5, 10, 20, and 40 mg/kg/day; minipump) exhibits a dose-proportional increase in both exposure and mitotic arrest in tumors in A2780-xenografted mice^[1].
MK-0731 (1 mg/kg/day; iv) has a T_1/2 of 1 hours, a CL of 66 mL/min•kg, and a V_ss of 3 L/kg for rats^[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