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A transformer-based strategy to develop RP20 as a potent RIPK2 inhibitor for acetaminophen-induced acute liver injury.

作者信息

Ouyang Liang

机构信息

Department of Biotherapy, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu 610041, China.

出版信息

Acta Pharm Sin B. 2025 Jul;15(7):3831-3832. doi: 10.1016/j.apsb.2025.06.003. Epub 2025 Jul 8.

DOI:10.1016/j.apsb.2025.06.003
PMID:40698128
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12278385/
Abstract
摘要

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A transformer-based strategy to develop RP20 as a potent RIPK2 inhibitor for acetaminophen-induced acute liver injury.一种基于变压器的策略，将RP20开发为对乙酰氨基酚诱导的急性肝损伤有效的RIPK2抑制剂。
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CMD-OPT model enables the discovery of a potent and selective RIPK2 inhibitor as preclinical candidate for the treatment of acute liver injury.CMD-OPT模型能够发现一种强效且具有选择性的RIPK2抑制剂，作为治疗急性肝损伤的临床前候选药物。
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Identification of a RIPK2-Regulated Gene Signature as a Candidate Biomarker for RIPK2 Activity and Prognosis in Prostate Cancer.鉴定一种RIPK2调控的基因特征作为前列腺癌中RIPK2活性和预后的候选生物标志物。
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Risk prediction of hepatotoxicity in paracetamol poisoning.对乙酰氨基酚中毒时肝毒性的风险预测
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A derivative of tanshinone IIA and salviadione, 15a, inhibits inflammation and alleviates DSS-induced colitis in mice by direct binding and inhibition of RIPK2.丹参酮IIA和丹参二酮的衍生物15a通过直接结合并抑制RIPK2来抑制炎症并减轻小鼠的右旋糖酐硫酸钠诱导的结肠炎。
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Paracetamol (acetaminophen) use in infants and children was never shown to be safe for neurodevelopment: a systematic review with citation tracking.对婴儿和儿童使用扑热息痛（对乙酰氨基酚）从未被证明对神经发育是安全的：一项有引文追踪的系统评价。
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IL-37 ameliorates acetaminophen-induced acute liver injury by limiting MAPK/NFκB signaling-mediated liver inflammation.白细胞介素-37通过限制丝裂原活化蛋白激酶/核因子κB信号介导的肝脏炎症来改善对乙酰氨基酚诱导的急性肝损伤。
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本文引用的文献

1
Hepatocyte-specific Mas activation enhances lipophagy and fatty acid oxidation to protect against acetaminophen-induced hepatotoxicity in mice.肝细胞特异性Mas激活增强脂质自噬和脂肪酸氧化，以保护小鼠免受对乙酰氨基酚诱导的肝毒性。
J Hepatol. 2023 Mar;78(3):543-557. doi: 10.1016/j.jhep.2022.10.028. Epub 2022 Nov 9.
2
Design of anti-inflammatory heparan sulfate to protect against acetaminophen-induced acute liver failure.设计具有抗炎活性的肝素硫酸盐以预防对乙酰氨基酚诱导的急性肝衰竭。
Sci Transl Med. 2020 Mar 18;12(535). doi: 10.1126/scitranslmed.aav8075.
3
Discovery of a First-in-Class Receptor Interacting Protein 2 (RIP2) Kinase Specific Clinical Candidate, 2-((4-(Benzo[]thiazol-5-ylamino)-6-(-butylsulfonyl)quinazolin-7-yl)oxy)ethyl Dihydrogen Phosphate, for the Treatment of Inflammatory Diseases.发现一种新型的受体相互作用蛋白 2（RIP2）激酶特异性临床候选药物，2-((4-(苯并噻唑-5-基氨基)-6-(-丁基磺酰基)喹唑啉-7-基)氧基)乙基二氢磷酸酯，用于治疗炎症性疾病。
J Med Chem. 2019 Jul 25;62(14):6482-6494. doi: 10.1021/acs.jmedchem.9b00575. Epub 2019 Jul 2.
4
Role of the inflammasome in acetaminophen-induced liver injury and acute liver failure.炎性小体在对乙酰氨基酚诱导的肝损伤和急性肝衰竭中的作用。
J Hepatol. 2017 Apr;66(4):836-848. doi: 10.1016/j.jhep.2016.11.017. Epub 2016 Nov 29.
5
A RIPK2 inhibitor delays NOD signalling events yet prevents inflammatory cytokine production.RIPK2 抑制剂延迟 NOD 信号事件，但可防止炎症细胞因子的产生。
Nat Commun. 2015 Mar 17;6:6442. doi: 10.1038/ncomms7442.
6
The mechanism underlying acetaminophen-induced hepatotoxicity in humans and mice involves mitochondrial damage and nuclear DNA fragmentation.在人类和小鼠中，醋氨酚导致肝毒性的机制涉及线粒体损伤和核 DNA 片段化。
J Clin Invest. 2012 Apr;122(4):1574-83. doi: 10.1172/JCI59755. Epub 2012 Mar 1.