PLK1-IN-4 是一种有效且具有选择性的PLK1抑制剂，IC50< 0.508 nM。PLK1-IN-4 对多种癌细胞具有广泛的抗增殖活性。PLK1-IN-4 诱导有丝分裂阻滞在 G2/M 期检查点，导致癌细胞凋亡 (apoptosis)。PLK1-IN-4 可用于肝细胞癌的研究。
| 生物活性 | PLK1-IN-4 is a potent and selectivePLK1inhibitor withIC50< 0.508 nM. PLK1-IN-4 has broad antiproliferative activity against a variety ofcancercell lines. PLK1-IN-4 induces mitotic arrest at the G2/M phase checkpoint, leading tocancercellapoptosis. PLK1-IN-4 can be used for researching hepatocellular carcinoma[1]. |
| IC50& Target | IC50:< 0.508 nM (PLK1)[1] |
体外研究
(In Vitro) | PLK1-IN-4 (compound 31) (0-5 μM; 48 hours) exhibits excellent antiproliferative activities against HCC cells[1].
PLK1-IN-4 (60 and 100 nM; 24 hours) induces abnormal spindle formation in HepG2 and HT-29 cells[1].
PLK1-IN-4 (10-300 nM; 0-48 hours) induces apoptosis in cancer cells through G2/M arrest[1].
PLK1-IN-4 (0-120 nM; 24 hours) increases phosphorylation of PLK1, histone H3 and NPM and decreases phosphorylation of Cdc2 in a dose-dependent manner[1].
Cell Proliferation Assay | Cell Line: | MDA-MB-231, HeLa, HCT 116, HT-29, HepG2, SMMC7721, A549 ,JeKo-1,K562, Karpas299, A375, DU-145 and L02[1] | | Concentration: | 0-5 μM | | Incubation Time: | 48 hours | | Result: | Exhibited excellent antiproliferative activities against HCC cells, with IC50s of 11.1 nM and 70.9 nM in HepG2 and SMMC7721 cells. |
Cell Cycle Analysis | Cell Line: | HepG2[1] | | Concentration: | 10, 30, 60, 100 and 300 nM | | Incubation Time: | 0, 12, 24, 36 and 48 hours | | Result: | Induced apoptosis in cancer cells through G2/M arrest. |
Western Blot Analysis | Cell Line: | HepG2[1] | | Concentration: | 0, 10, 30, 60, 90 and 120 nM | | Incubation Time: | 24 hours | | Result: | Increased phosphorylation of PLK1, histone H3 and NPM and decreased phosphorylation of Cdc2 in a dose-dependent manner. |
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体内研究
(In Vivo) | PLK1-IN-4 exhibits low metabolic stability in species of human, mouse, dog and monkey, with CLhepof 74.3, 330.9, 61.5 and 196.5 mL/min/kg, respectively[1].
PLK1-IN-4 (30 mg/kg; tail vein injection; once or twice daily, for 12 days) suppresses tumor growth in a dose dependent manner[1].
Pharmacokinetic Parameters of PLK1-IN-4 in male ICR mouse[1].
| IV (5 mg/kg) | | C0(ng/mL) | 1790 | | T1/2(h) | 1.47 | | MRT0-inf(h) | 0.808 | | MRT0-t(h) | 0.704 | | AUC0-t(ng·h/mL) | 767 | | AUC0-inf(ng·h/mL) | 776 | | CL (mL/min/kg) | 107 | | VdSS(L/kg) | 107 |
| Animal Model: | Male nu/nu BALB/c mice (4-6 weeks; injected with HepG2 cells)[1] | | Dosage: | 30 mg/kg | | Administration: | Tail vein injection; once or twice daily, for 12 days | | Result: | Suppressed tumor growth in a dose dependent manner, and the tumor growth inhibition (TGI) values were 120.0% and 135.2% at doses of 30 mg/kg once daily and 30 mg/kg twice daily, respectively. |
| Animal Model: | ICR mouse[1] | | Dosage: | 5 mg/kg | | Administration: | IV; single (Pharmacokinetics Analysis) | | Result: | Exhibited a short half-life (T1/2) of 1.47 h, moderate exposure with an area under the curve (AUC0-inf) of 776 ng·h/mL and volume of distribution at steady state (Vdss) of 5.21 L/kg. |
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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. |
