Advances in RIPK1 kinase inhibitors

Lu Chen; Xiaoqin Zhang; Yaqing Ou; Maoyu Liu; Dongke Yu; Zhiheng Song; Lihong Niu; Lijuan Zhang; Jianyou Shi

doi:10.3389/fphar.2022.976435

Advances in RIPK1 kinase inhibitors

Front Pharmacol. 2022 Sep 28:13:976435. doi: 10.3389/fphar.2022.976435. eCollection 2022.

Authors

Lu Chen¹, Xiaoqin Zhang², Yaqing Ou³, Maoyu Liu⁴, Dongke Yu¹, Zhiheng Song^{1

2

3

4

5

6}, Lihong Niu^{1

2

3

4

5

6}, Lijuan Zhang¹, Jianyou Shi⁴

Affiliations

¹ College of Pharmacy, Chengdu University of Traditional Chinese Medicine, Chengdu, China.
² Department of Critical Care Medicine, Sichuan Academy of Medical Sciences, Sichuan Provincial People's Hospital, Affiliated Hospital of University of Electronic Science and Tec1hnology of China, Chengdu, Sichuan, China.
³ Department of Pharmacy, The Affiliated Chengdu 363 Hospital of Southwest Medical University, Chengdu, Sichuan, China.
⁴ Personalized Drug Therapy Key Laboratory of Sichuan Province, Department of Pharmacy, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu, China.
⁵ Suzhou University of Science and Technology, Suzhou, Jiangsu, China.
⁶ Institute of Laboratory Animal Sciences, Academy of Medical Sciences and Sichuan Provincial People's Hospital, Chengdu, Sichuan, China.

Abstract

Programmed necrosis is a new modulated cell death mode with necrotizing morphological characteristics. Receptor interacting protein 1 (RIPK1) is a critical mediator of the programmed necrosis pathway that is involved in stroke, myocardial infarction, fatal systemic inflammatory response syndrome, Alzheimer's disease, and malignancy. At present, the reported inhibitors are divided into four categories. The first category is the type I ATP-competitive kinase inhibitors that targets the area occupied by the ATP adenylate ring; The second category is type Ⅱ ATP competitive kinase inhibitors targeting the DLG-out conformation of RIPK1; The third category is type Ⅲ kinase inhibitors that compete for binding to allosteric sites near ATP pockets; The last category is others. This paper reviews the structure, biological function, and recent research progress of receptor interaction protein-1 kinase inhibitors.

Keywords: RIP1 (RIPK1); inhibitor; necrosis; programmed necrosis; receptor interacting protein 1 (RIP1).

Publication types

Review