Discovery and preclinical profile of YK-2168, a differentiated selective CDK9 inhibitor in clinical development

被引：0

作者：

Liu, Yingchun ^{[2
]}

Xu, Zhaobing ^{[2
]}

Hu, Lihong ^{[2
]}

Xia, Li ^{[3
]}

Li, Qi ^{[3
]}

Zhou, Wang ^{[1
]}

Chen, Yadong ^{[1
]}

Li, Wei ^{[3
]}

Jiang, Wen ^{[2
]}

Zhu, Xingxun ^{[2
]}

Gao, Xiao ^{[2
]}

Xia, Yuanfeng ^{[3
]}

Zhu, Zhenzhen ^{[3
]}

Chen, Shuhui ^{[3
]}

Ding, Charles Z. ^{[3
]}

机构：

[1] Nanjing Damei Biopharmaceut Co Ltd, Room 226,Second Floor Comprehens Off Bldg Chem Ind, Nanjing 210023, Jiangsu, Peoples R China

[2] WuXi AppTec, 666 Gaoxin Rd, Wuhan 430075, Peoples R China

[3] WuXi AppTec, 288 Fute Zhong Rd, Shanghai 200131, Peoples R China

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2024年 / 112卷

关键词：

CDK inhibitor; CDK9 selective inhibitor; Azaindole; AZD4573; POTENT;

D O I：

10.1016/j.bmcl.2024.129941

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Emerging clinical evidence indicates that selective CDK9 inhibition may provide clinical benefits in the management of certain cancers. Many CDK9 selective inhibitors have entered clinical developments, and are being investigated. No clear winner has emerged because of unforeseen toxicity often observed in clinic with these agents. Therefore, a novel agent with differentiated profiles is still desirable. Herein, we report our design, syntheses of a novel azaindole series of selective CDK9 inhibitors. SAR studies led to a preclinical candidate YK2168. YK2168 exhibited improved CDK9 selectivity over AZD4573 and BAY1251152; also showed differentiated intravenous PK profile and remarkable solid tumor efficacy in a mouse gastric cancer SNU16 CDX model in preclinical studies. YK-2168 is currently in clinical development in China (CTR20212900).

引用

页数：5

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