Senexin C 是一种选择性和具有口服活性的CDK8/19抑制剂。Senexin C 显示出强烈的肿瘤富集药代动力学 (PK) 谱和肿瘤药效学 (PD) 标志物反应。Senexin C 抑制 MV4-11 白血病细胞的生长具有良好的耐受性。
| 生物活性 | Senexin C is a selective and orally activeCDK8/19inhibitor. Senexin C shows a strong tumor-enrichment pharmacokinetic (PK) profile and tumor-pharmacodynamic (PD) marker responses. Senexin C inhibits the growth of MV4-11 leukemia cells with good tolerability[1]. |
| IC50& Target[1] | CDK8/CycC 3.6 nM (IC50) | CDK19/CycC 2.9 nM (Kd) | CDK8/CycC 1.4 nM (Kd) |
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体外研究
(In Vitro) | Senexin C (compound 20a) exhibits potent CDK8/19 inhibitory activity with high selectivity (IC50s of 56 and 108 nM for 293-NFκB-Luc and MV4-11-Luc cells, respectively)[1].
Senexin C (2 μM) shows potency in different kinase assays (IC50= 3.6 nM for CD8/CycC, Kd=1.4 nM for CD8/CycC, Kd=2.9 nM for CDK19/CycC)[1].
Senexin C (1 μM, 3 h) shows inhibition on CDK8/19 dependent cellular gene expression[1].
RT-PCR[1] | Cell Line: | 293 cells | | Concentration: | 1 μM | | Incubation Time: | 3 h | | Result: | Showed inhibition on CDK8/19 dependent cellular gene expression. |
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体内研究
(In Vivo) | Senexin C (2.5 mg/kg, i.v.; 100 mg/kg, p.o.) shows good oral bioavailability[1].
Senexin C (40 mg/kg; p.o.; twice daily for 4 weeks) suppresses the systemic growth of MV4-11 AML with good tolerability[1].Pharmacokinetic Parameters of Senexin C in eight-week-old female Balb/c mice[1].
| parameters | iv (2.5 mg/kg) | po (100 mg/kg) | | plasma | tumor | plasma | tumor | | C0(μg/mL) | 503 | | | | | Kel(h-1) | 0.93 | 0.06 | 0.2 | 0.1 | | T1/2(h) | 0.75 | 12.1 | 3.53 | 7.27 | | Tmax(h) | | 0.58 | 12 | 12 | | Cmax(ng/mL or ng/g) | | 488 | 144 | 5728 | | AUC0-24 h (ng x h/ml or ng x h/g) | 331 | 6408 | 2182 | 88,600 | | F% | | | 16.5% | 34.6% |
Eight-week-old female Balb/c mice ( CT26 tumor mode), 2.5 mg/kg, i.v.(2.5 mg/mL Senexin C solution in 5% dextrose); 100 mg/kg, p.o.(10 mg/mL Senexin C solution in 30% propylene glycol/70% PEG-400 vehicle) [1].
| Animal Model: | eight-week-old female Balb/c mice ( CT26 tumor mode)[1] | | Dosage: | 2.5 mg/kg (10 mL/kg of 2.5 mg/mL Senexin C solution in 5% dextrose), 100 mg/kg (10 mL/kg of 10 mg/mL Senexin C solution in 30% propylene glycol/70% PEG-400 vehicle) | | Administration: | 2.5 mg/kg, i.v.; 100 mg/kg, p.o. | | Result: | Showed good oral bioavailability. |
| Animal Model: | eight-week-old female NSG mice ( AML model)[1] | | Dosage: | 40 mg/kg | | Administration: | p.o.; twice daily, 4 weeks | | Result: | Suppressed the systemic growth of MV4-11 AML with good tolerability. |
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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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