CDK8-IN-13 is a potent, selective, and orally active CDK8 inhibitor with an IC50 value of 51.9nM[1]. CDK8-IN-13 has been widely used as a lead compound to analyze the binding mode with the active site of CDK8 in molecular docking experiments, and to develop a series of CDK8 inhibitors[2].
In vitro, CDK8-IN-13 treatment (10µM) for 12 hours significantly inhibited the phosphorylation of STAT1 at S727 and STAT5 at S726 in HCT-116 cells[1].
In vivo, CDK8-IN-13 treatment via oral administration at a dose of 80mg/kg/day for 15 days significantly inhibited tumor growth in the C1498 xenograft mouse model, without causing significant weight loss[1].
References:
[1] Zhang X X, Yan Y Y, Ma X, et al. Discovery of a novel oral type Ⅰ CDK8 inhibitor against acute myeloid leukemia[J]. European Journal of Medicinal Chemistry, 2023, 251: 115214.
[2] Chen Z, Wang Q, Yan Y Y, et al. Discovery of novel and potent CDK8 inhibitors for the treatment of acute myeloid leukaemia[J]. Journal of Enzyme Inhibition and Medicinal Chemistry, 2024, 39(1): 2305852.
CDK8-IN-13是一种强效、选择性且口服有效的CDK8抑制剂，IC50值为51.9nM[1]。CDK8-IN-13已被广泛用作先导化合物，用于在分子对接实验中分析与CDK8活性位点的结合模式，并用于开发一系列CDK8抑制剂[3]。
在体外，使用10μM的CDK8-IN-13处理HCT-116细胞12小时，显著抑制了STAT1在S727位点和STAT5在S726位点的磷酸化[1]。
在体内，每日口服80mg/kg剂量的CDK8-IN-13，连续15天，显著抑制了C1498异种移植小鼠模型中的肿瘤生长，且未引起显著的体重减轻[1]。