1b:I[76749,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1c:I[3486,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1d:I[41892,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1e:I[17707,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 1f:I[66528,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 20:I[63176,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 21:I[87099,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 22:I[26200,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"Group"] 23:I[23365,["/_next/static/chunks/0383663887945ae7.js","/_next/static/chunks/df7e62179e4ae938.js","/_next/static/chunks/acf71181277ecf85.js","/_next/static/chunks/63561dcd578bd4db.js","/_next/static/chunks/5bf36002c846d2d8.js","/_next/static/chunks/b24fef6e58c9b2f5.js","/_next/static/chunks/ea1fda2cc52e974e.js"],"default"] 24:T463,CDK8 is a transcriptional cyclin-dependent kinase and considered as a potential target in colon cancer therapeutics. Here, a novel selective CDK8 inhibitor was identified against colon cancer in vivo. Specifically, based on the structural information of the sorafenib-bound CDK8 structure, a series of novel 2-amino-pyridine derivatives were designed, synthesized, and evaluated. Among them, compound 29 showed strong inhibitory activity against CDK8 with an IC₅₀ value of 46 nM and favorable selectivity. And there is an apparent interaction between the endogenous or overexpressed CDK8 and biotinylated-29. This compound exhibited antiproliferation potency on colon cancer cell lines with a high CDK8 expression level, suppressed the activation of WNT/β-catenin and transcriptional activity of the TCF family, and induced G1 phase arrested in HCT-116 cells. In addition, this compound showed potent activity against sorafenib-resistant HCT-116 cells. What's more, it exhibited low toxicity and suitable pharmacokinetic (PK) profiles and showed preferable antitumor effects in vivo.

Yao Yao Yan

Publications