CDK/HDAC-IN-2 是一种有效的HDAC/CDK双重抑制剂，对于 HDAC1, HDAC2, HDAC3, HDAC6,8, CDK1, CDK2, CDK4,6,7,IC50分别为 6.4, 0.25, 45, >1000, 8.63, 0.30, >1000 nM。CDK/HDAC-IN-2 显示出优异的抗增殖活性。CDK/HDAC-IN-2 诱导细胞凋亡 (apoptosis) 和细胞周期停滞在 G2/M 期。CDK/HDAC-IN-2 显示出强大的抗肿瘤功效。
| 生物活性 | CDK/HDAC-IN-2 is a potentHDAC/CDKdual inhibitor withIC50of 6.4, 0.25, 45, >1000, 8.63, 0.30, >1000 nM forHDAC1,HDAC2,HDAC3,HDAC6,8,CDK1,CDK2,CDK4,6,7, respectively. CDK/HDAC-IN-2 shows excellent antiproliferative activities. CDK/HDAC-IN-2 inducesapoptosisand cell cycle arrest at G2/M phase. CDK/HDAC-IN-2 shows potent antitumor efficacy[1]. |
| IC50& Target[1] | HDAC1 6.4 nM (IC50) | HDAC2 0.25 nM (IC50) | HDAC3 45 nM (IC50) | HDAC6 >1000 nM (IC50) | HDAC8 >1000 nM (IC50) | CDK1 8.63 nM (IC50) | CDK2 0.30 μM (IC50) | CDK4 >1000 nM (IC50) | CDK6 >1000 nM (IC50) | CDK7 >1000 nM (IC50) |
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体外研究
(In Vitro) | CDK/HDAC-IN-2 (compound 7c) shows antiproliferative activity with IC50s of 0.71, 1.20, 1.83, 4.19, 7.76, 4.47 μM for HCT116, A375, Hela, H460, SMMC7721, NIH 3T3 cells, respectively[1].
CDK/HDAC-IN-2 (24 h) shows anti-migration ability in A375 and H460 cells[1].
CDK/HDAC-IN-2 (0.5, 1, 2 μM) induces apoptosis and cell cycle arrest at G2/M phase[1].
CDK/HDAC-IN-2 accelerates intracellular ROS accumulation, leading to cancer cell death[1].
Cell Cycle Analysis[1] | Cell Line: | A375, HCT116, H460, Hela cells | | Concentration: | 0.5, 1, 2 μM | | Incubation Time: | 24 h | | Result: | Induced cell cycle arrest at G2/M phase. |
Apoptosis Analysis[1] | Cell Line: | A375, HCT116, H460, Hela cells | | Concentration: | 0.5, 1, 2 μM | | Incubation Time: | 48 h | | Result: | Induced cell apoptosis with the apoptosis rates of A375, HCT116 cells of 97.22%, 60.6%, respectively. |
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体内研究
(In Vivo) | CDK/HDAC-IN-2 (12.5, 25 mg/kg; IP; once daily for 21 days) shows antitumor efficacy in the HCT116 xenograft model (TGI= 51.0%)[1].
Pharmacokinetic Parameters of CDK/HDAC-IN-2 in ICR male mice[1].
| compound | 7c | | Dose (mg/kg) | 20 | | administration | i.p. | | t1/2(h) | 2.61 | | Tmax(h) | 2.00 | | Cmax(h) | 7570 | | AUC0-∞(ng h/mL) | 30700 | | MRT0-∞(ng h/mL) | 3.31 | | F (%) | 63.6 |
ICR male mice; 20 mg/kg, i.p. [1].
| Animal Model: | ICR male mice[1] | | Dosage: | 20 mg/kg | | Administration: | IP | | Result: | Showed good Pharmacokinetic parameters with bioavailability of F= 63.6%. |
| Animal Model: | 5-6 weeks, BALB/c female mice (HCT116 xenograft nude mice models)[1] | | Dosage: | 12.5, 25 mg/kg | | Administration: | IP, once daily for 21 days | | Result: | Effectively inhibited the growth of HCT116 xenograft tumors tumor growth inhibitions (TGI) at 12.5 and 25 mg/kg of 37.0% and 51.0%, respectively. |
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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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