ZLMT-12 (compound 35) 是他克宁衍生物，是一种有效的CDK2/9抑制剂，抑制 CDK9 和 CDK2 的IC50值分别为 0.002 和 0.011 μM。ZLMT-12 对AChE(IC50=19.023 μM) 和BuChE(IC50=2.768 μM) 有弱抑制作用。ZLMT-12 具有低毒和抗增殖活性。ZLMT-12 诱导细胞凋亡 (apoptosis)，阻滞细胞周期在 S 期和 G2/M 期。
| 生物活性 | ZLMT-12 (compound 35), tacrine derivatives, is a potent, orally activeCDK2/9inhibitor withIC50values of 0.002 and 0.011 μM forCDK9andCDK2, respectively. ZLMT-12 has a weak inhibitory effect onAChE(IC50=19.023 μM) andBChE(IC50=2.768 μM). ZLMT-12 has low toxicity and antiproliferative activity. ZLMT-12 inducesapoptosisand arrests the cell cycle in the S phase and G2/M phase[1]. |
| IC50& Target[1] | CDK9 0.002 μM (IC50) | CDK2 0.011 μM (IC50) | BChE 2.768 μM (IC50) | AChE 19.023 μM (IC50) |
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体外研究
(In Vitro) | ZLMT-12 (compound 35; 500 nM; 72 h) has antiproliferative activity in cancer cells[1].
ZLMT-12 (500 nM; 72 h) induces apoptosis and arrests the cell cycle in the S phase and G2/M phase[1].
Cell Viability Assay[1] | Cell Line: | HCT116, SW480, A549, and MCF-7 cells | | Concentration: | 500 nM | | Incubation Time: | 72 hours | | Result: | Inhibited cell proliferative with GI50values of 0.029, 0.328, 0.051, and 0.109 μM for HCT116, SW480, A549, and MCF-7 cells, respectively. |
Apoptosis Analysis[1] | Cell Line: | HCT116 cells | | Concentration: | 10 and 20 nM | | Incubation Time: | 48 hours | | Result: | Increased apoptotic cells rate from 9.22% in the control to 23.77% at 10 nM and increased apoptotic cells rate to 46.2% at 20 nM. |
Cell Cycle Analysis[1] | Cell Line: | HCT116 cells | | Concentration: | 10 and 20 nM | | Incubation Time: | 48 hours | | Result: | Increased the percentage of the S phase from 31.43% to 42.75% (10 nM) and 49.38% (20 nM) respectively, and the percentage of the G2/M phase from 6.39% to 10.60% (10 nM) and 13.11% (20 nM), respectively. |
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体内研究
(In Vivo) | ZLMT-12 (compound 35; 10 mg/kg; p.o.; daily, for 21 d) has antitumor efficacy and inhibits tumor growth, without causing liver harm in the HCT116 xenograft model[1].
| Animal Model: | Male BALB/cA-nu mice with HCT116 xenografts (18-25 g, 6-8 weeks of age)[1] | | Dosage: | 10 mg/kg | | Administration: | Oral administration; daily, for 21 days | | Result: | Inhibited tumor growth with GI (tumor volume growth inhibition)=47.66% and TGI (tumor weight growth inhibition)=62.39%.
Exhibited no significant changes in behavior or body weight in mice.
Had no obvious liver injury.
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| Animal Model: | Male Sprague-Dawley rats (240±20 g)[1] | | Dosage: | 2 mg/kg (i.v.) and 20 mg/kg (p.o.) (Pharmacokinetic Analysis) | | Administration: | Intravenous injection and oral administration; once | | Result: | 1.19| Parameter | 2 mg/kg (i.v.) | 20 mg/kg (p.o.) | | T1/2(h) | 0.461 | 1.77 | | Tmax(h) | 0.083/td> | 1.00 | | Cmax(ng/mL) | 206 | 67.8 | | AUCo-t(h*ng/mL) | 110 | 302 | | AUCo-∞(h*ng/mL) | 115 | 316 | | CL (L/h/kg) | 18.7 | | | Vss(L/Kg) | 12.6 | | | F (%) | | 27.47 |
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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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