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April 8, 2024Open Access

Development of a First-in-Class RIPK1 Degrader to Enhance Antitumor Immunity

Jin Wang Dong Lu Xin Yu Xiaoli Qi Hanfeng Lin Bryan Latrell Holloman Feng Jin Longyong Xu Lang Ding Weiyi Peng Meng C. Wang Xi Chen

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Abstract

The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and has emerged as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain, we harnessed proteolysis targeting chimera (PROTAC) technology to develop a first-in-class RIPK1 degrader, LD4172. LD4172 exhibited potent and selective RIPK1 degradation both

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Wang et al. (2024) studied this question.

synapsesocial.com/papers/68e70002b6db64358767a361 https://doi.org/10.21203/rs.3.rs-4156736/v1

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