CDK4/6-IN-10 是一种有效的、选择性的和具有口服活性的CDK4和CDK6抑制剂，其IC50值分别为 22 nM 和 10 nM。CDK4/6-IN-10 显示出抗肿瘤活性。CDK4/6-IN-10 具有研究多发性骨髓瘤 (MM) 的潜力。

CDK4/6-IN-10 is a potent, selective and orally active CDK4 and CDK6 inhibitor with IC 50 s of 22 nM and 10 nM, respectively. CDK4/6-IN-10 shows antitumor activity. CDK4/6-IN-10 has the potential for the research of Multiple myeloma (MM) [1].

CDK4/6-IN-10 (compouns 32) (1 μM) shows kinase selectivity with IC 50 s of 22 nM and 10 nM for CDK4 and CDK6, respectively [1]. CDK4/6-IN-10 (72 h) shows antiproliferative activity (GI 50 s of 2.028, 5.802, 2.286, 2.238, 1.526, 11.381 μM for RPMI-8226, U266, K562, HL-60, 22RV1, HEK-293 cells, respectively) [1]. CDK4/6-IN-10 (0, 1.5, 3, 6 μM, 24 h) induces cell cycle arrest at the G1 phase in a concentration-dependent manner [1]. CDK4/6-IN-10 ( 0, 1, 2, 3 μM, 24 h) induces apoptosis of RPMI-8226 cells in a concentration-dependent manner [1]. CDK4/6-IN-10 (0, 1.5, 3, 6 μM, 24 h) reduces the CDK4/6 activity by decreases the expression level of p-RB, c-MYC and BCL-2 [1]. Cell Proliferation Assay [1] Cell Line: RPMI-8226, U266, K562, HL-60, 22RV1, HEK-293 cells Concentration: Incubation Time: 72 h Result: Shows antiproliferative activity (GI 50 s of 2.028, 5.802, 2.286, 2.238, 1.526, 11.381 μM for RPMI-8226, U266, K562, HL-60, 22RV1, HEK-293 cells, respectively). Cell Cycle Analysis [1] Cell Line: RPMI-8226 cells Concentration: 0, 1.5, 3, 6 μM Incubation Time: 24 h Result: Cells were arrested at the G1 phase in a concentration-dependent manner. Apoptosis Analysis [1] Cell Line: RPMI-8226 cells Concentration: 0, 1.5, 3, 6 μM Incubation Time: 24 h Result: Reduced the CD4/K activity by decreased the expression level of p-RB, c-MYC and BCL-2.

CDK4/6-IN-10 (1000, 5000, 10000 mg/kg; p.o.) shows safety profile with LD 50 much higher than 10,000 mg/kg [1]. CDK4/6-IN-10 (10 mg/kg; p.o.) shows oral bioavailability (F=51%) in SD rats [1]. CDK4/6-IN-10 (100, 200 mg/kg; p.o., once a day for 19 days) shows antitumor potency and favorable safety profile [1]. Pharmacokinetic Parameters of CDK4/6-IN-10 in SpragueeDawley rats [1]. Compd Admin. C max (ng/mL) AUC 0-t (h·ng/mL) MRT 0-t (h) T max (h) t 1/2 (h) CL (mL/h/kg) F (%) 32 i.v. 355 960 5.9 0.033 8.9 641 - p.o. 257 4,878 12.8 10.7 >24 524 51

(< 1 mg/ml refers to the product slightly soluble or insoluble )
Powder: -20°C for 3 years
In solvent: -80°C for 2 years