Senexin C

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

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。

Senexin C is a selective and orally active CDK8/19 inhibitor. 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.

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).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).Senexin C (1 μM, 3 h) shows inhibition on CDK8/19 dependent cellular gene expression.RT-PCR Cell Line:293 cells Concentration:1 μM Incubation Time:3 h Result:Showed inhibition on CDK8/19 dependent cellular gene expression.

Senexin C (2.5 mg/kg, i.v.; 100 mg/kg, p.o.) shows good oral bioavailability.Senexin C (40 mg/kg; p.o.; twice daily for 4 weeks) suppresses the systemic growth of MV4-11 AML with good tolerability.Pharmacokinetic Parameters of Senexin C in eight-week-old female Balb/c mice.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).Animal Model:eight-week-old female Balb/c mice ( CT26 tumor mode)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) 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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Cell Cycle/DNA Damage

CDK

CDK

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2375554-02-0

449.55

C28H27N5O

>98% (HPLC)

In Vitro:?DMSO 中的溶解度 : 33.33 mg/mL (74.14 mM; ultrasonic and warming and heat to 160°C)

N#CC=1C=CC2=NC=CC(NCCC=3C=CC4=CC(=CC=C4C3)C(=O)N5CCN(C)CC5)=C2C1

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(-20℃)

With Ice Pack

≥ 2 years