CDK4/6-IN-15 是一种口服有效和选择性CDK4/6抑制剂。CDK4/6-IN-15 能有效抑制癌细胞生长。CDK4/6-IN-15 将细胞周期阻滞在 G1 期，并抑制视网膜母细胞瘤肿瘤抑制蛋白 (Rb) 在 S780 位点的磷酸化和 E2 因子 (E2F) 调控的基因表达。
| 生物活性 | CDK4/6-IN-15 is an orally active and selectiveCDK4/6inhibitor. CDK4/6-IN-15 potently inhibitscancercells growth. CDK4/6-IN-15 arrests cell cycle at G1 phase and suppresses retinoblastoma tumour suppressor protein (Rb) phosphorylation at S780 and E2 factor (E2F)-regulated gene expression[1]. |
| IC50& Target[1] | CDK4 3 nM (IC50) | CDK6 0.279 μM (IC50) | CDK2 3.335 μM (IC50) |
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体外研究
(In Vitro) | CDK4/6-IN-15 (化合物 91) (10 μM; 24 h) 还能有效抑制 FLT3 和 MYLK4，抑制率>90%[1]。
CDK4/6-IN-15 (0-5 μM; 72 h) 选择性抑制肿瘤细胞增殖，GI50分别为 0.107 μM (MV4-11) 和 0.325 μM (MDA-MB-453)[1]。
CDK4/6-IN-15 (0.1-1 μM; 24 h) 阻滞 Rb 阳性细胞 MV4-11 和 MDA-MB-453 细胞的细胞周期在 G1 期[1]。
CDK4/6-IN-15 (0.1-1 μM 或 0.3-3 μM; 24-96 h) 诱导 MV4-11 和 MDA-MB-453 细胞凋亡[1]。
CDK4/6-IN-15 (0.1-3.3 μM; 4-24 h) 抑制 Rb 的磷酸化[1]。
Apoptosis Analysis[1] | Cell Line: | MV4-11 and MDA-MB-453 cells | | Concentration: | 0.1 μM, 0.5 μM, and 1 μM for MV4-11; 0.3 μM, 0.6 μM, and 3.3 μM for MDA-MB-453 cells | | Incubation Time: | 24 h, 48 h, 72 h, and 96 h | | Result: | Induced cell apoptosis via arresting cell cycle at G1 accompanied with Rb) phosphorylation suppression and E2F-regulated gene expression decreases. |
Western Blot Analysis[1] | Cell Line: | MV4-11 (GI50=0.107 μM) and MDA-MB-453 (GI50=0.325 μM) | | Concentration: | 1×, 5×, 10× GI50 | | Incubation Time: | 4 h, 12 h, and 24 h | | Result: | Resulted inhibition of Rb phosphorylation at S780. |
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体内研究
(In Vivo) | CDK4/6-IN-15 (化合物 91) (静脉注射 2 mg/kg 或口服 10 mg/kg; 单剂量) 在健康雄性成年 BALB/c 小鼠 (20-25 g) 和在 (静脉注射 5 mg/kg 或口服 20 mg/kg; 单剂量) 雄性白化 Wistar 大鼠 (250-350 g) 中，显示出相当的口服吸收特性[1]。
药代动力学分析[1]
| Route | Dose (mg/kg) | CL (mL/min/kg) | Vss(L/kg) | AUC (μM·h) | Cmax(μM) | Tmax(h) | t1/2(h) | F (%) | | rat | IV | 5 | 155 | 27.5 | 1.2 | 1.4 | / | 2.1 | / | | PO | 20 | / | / | 4.4 | 0.3 | 4.3 | 20.3 | 95 | | mouse | IV | 2 | 90 | 15.7 | 0.7 | 1.3 | / | 2.9 | / | | PO | 10 | / | / | 4.3 | 0.6 | 2.5 | 2.7 | 129 |
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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. |
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