CDK4/6-IN-14 是一种有效且高度选择性的CDK4和CDK6(CDK) 抑制剂，IC50分别为 10 nM 和 16 nM。CDK4/6-IN-14 的选择性是 CDK 1、2、7 和 9 的 60 多倍，并且在其他 205 种激酶中表现出高选择性。
| 生物活性 | CDK4/6-IN-14 is a potent and highly selectiveCDK4andCDK6(CDK) inhibitor withIC50s of 10 nM and 16 nM, respectively. CDK4/6-IN-14 exhibits more than 60-fold selectivity over CDKs 1, 2, 7, and 9, and shows high selectivity among other 205 kinases[1]. |
| IC50& Target[1] | CDK4 10 nM (IC50) | CDK6 16 nM (IC50) | CDK1 >10000 nM (IC50) | CDK2 1045 nM (IC50) | CDK7 2595 nM (IC50) | CDK9 2664 nM (IC50) |
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体外研究
(In Vitro) | CDK4/6-IN-14 (compound 42; 1-6 μM; 5 days) exhibits potent inhibitory activity against the proliferation of breast cancer MCF-7, T47D, and ZR-75-1 cell lines. CDK4/6-IN-14 significantly inhibits growth and clone formation of MCF-7 and T47D cells[1].
CDK4/6-IN-14 (compound 42; 1-6 μM) arrests the cell cycle at the G1 phase of MCF-7 and T47D cells in the dose-dependent manner[1].
CDK4/6-IN-14 (compound 42; 1-6 μM; 24 hours) significantly inhibits the phosphorylation of retinoblastoma (RB), while the expression of RB protein was almost unchanged. In addition, CDK4/6-IN-14 exhibits a concentration-dependent effect to decrease the level of c-MYC and cyclin D1[1].
Cell Cytotoxicity Assay[1] | Cell Line: | MCF-7 and T47D cells | | Concentration: | 1 μM, 2 μM, 4 μM (T47D cells); 1.5 μM, 3 μM, 6 μM (MCF-7 cells) | | Incubation Time: | 5 days | | Result: | Significantly inhibited growth and clone formation of MCF-7 and T47D cells. |
Western Blot Analysis[1] | Cell Line: | MCF-7 and T47D cells | | Concentration: | 1 μM, 2 μM, 4 μM (T47D cells); 1.5 μM, 3 μM, 6 μM (MCF-7 cells) | | Incubation Time: | 24 hours | | Result: | Significantly inhibited the phosphorylation of RB. |
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体内研究
(In Vivo) | CDK4/6-IN-14 (compound 42; 100-150 mg/kg; p.o; once a day; for 23 days) significantly inhibits tumor growth of the MCF-7 xenograft model[1].
CDK4/6-IN-14 (compound 42) exhibits a suitable t1/2 of intravenous and oral administration (2.62 and 3.59 h, respectively). Moreover, the oral bioavailability of CDK4/6-IN-14 is 43%[1].
Pharmacokinetic Parameters of CDK4/6-IN-14 (Compound 42) in Sprague–Dawley Rats[1].
| admin. | Cmax(ng/mL) | AUC0-∞(h × ng/mL) | MRT0-∞(h) | Tmax(h) | t1/2(h) | F (%) | | IV | 290.52 | 372.56 | 3.50 | 0.033 | 2.62 | | | PO | 144.11 | 1612.18 | 9.11 | 6 | 3.59 | 43 |
Dose: i.v. at 1 mg/kg; p.o. at 10 mg/kg [1]
| Animal Model: | BALB/c nude mice bearing MCF-7 cells[1] | | Dosage: | 100 mg/kg, 150 mg/kg | | Administration: | Orally administertion; once a day; for 23 days | | Result: | Significantly inhibited tumor growth of the MCF-7 xenograft model. |
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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. |
