Bibliographic Details
| Title: |
Development of a RIPK1 degrader to enhance antitumor immunity. |
| Authors: |
Yu, Xin, Lu, Dong, Qi, Xiaoli, Paudel, Rishi Ram, Lin, Hanfeng, Holloman, Bryan L., Jin, Feng, Xu, Longyong, Ding, Lang, Peng, Weiyi, Wang, Meng C., Chen, Xi, Wang, Jin |
| Source: |
Nature Communications; 12/16/2024, Vol. 15 Issue 1, p1-14, 14p |
| Subject Terms: |
RECEPTOR-interacting proteins, MEDICAL sciences, IMMUNE checkpoint proteins, IMMUNE checkpoint inhibitors, LIFE sciences |
| Abstract: |
The scaffolding function of receptor interacting protein kinase 1 (RIPK1) confers intrinsic and extrinsic resistance to immune checkpoint blockades (ICBs) and emerges as a promising target for improving cancer immunotherapies. To address the challenge posed by a poorly defined binding pocket within the intermediate domain of RIPK1, here we harness proteolysis targeting chimera (PROTAC) technology to develop a RIPK1 degrader, LD4172. LD4172 exhibits potent and selective RIPK1 degradation both in vitro and in vivo. Degradation of RIPK1 by LD4172 triggers immunogenic cell death, enhances tumor-infiltrating lymphocyte responses, and sensitizes tumors to anti-PD1 therapy in female C57BL/6J mice. This work reports a RIPK1 degrader that serves as a chemical probe for investigating the scaffolding functions of RIPK1 and as a potential therapeutic agent to enhance tumor responses to ICBs therapy. It has been shown that targeting receptor-interacting protein kinase 1 (RIPK1) can improve response to immune checkpoint inhibitors. Here, using PROTAC technology, the authors report the design and characterization of a RIPK1 degrader, enhancing anti-tumor immunity in preclinical cancer models. [ABSTRACT FROM AUTHOR] |
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| Database: |
Complementary Index |
