Discovery of HDM2004, a potent, selective and orally bioavailable HPK1 inhibitor for tumor immunotherapy.

Zhimin Zhang¹, Minhao Huang², Jingwen E¹, Zhiping Zhang¹, Tao Deng¹, Yacheng Yang¹, Yina Sun², Junjie Zou², Xiaohua Zhang¹, Tingni Chen¹, Dongzhou Liu³

¹Global R&D Center, Huadong Medicine, Hangzhou, 310011, China.

²Shenzhen Jingtai Technology Co., Ltd. (XtalPi), Shenzhen, 518045, China.

³Global R&D Center, Huadong Medicine, Hangzhou, 310011, China. Electronic address: jefferydliu@eastchinapharm.com.

PubMed DOI

Abstract

Hematopoietic progenitor kinase 1 (HPK1) has emerged as a compelling target for tumor immunotherapy due to its pivotal role in regulating key cellular processes, including survival, migration, apoptosis, and autophagy. In this comprehensive study, we characterized the pharmacological profile of a novel HPK1 inhibitor HDM2004 (compound 37). Through systematic structure-activity relationship (SAR) o…

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