ASK1抑制剂的发现和开发。

Q1 Pharmacology, Toxicology and Pharmaceutics

Progress in medicinal chemistry Pub Date : 2020-01-01 Epub Date: 2020-04-22 DOI:10.1016/bs.pmch.2020.02.001

Reginald Brys, Karl Gibson, Tanja Poljak, Steven Van Der Plas, David Amantini

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引用次数: 12

摘要

丝裂原活化蛋白激酶(MAPKs)如c-Jun n-末端激酶(JNK)和p38的异常激活是涉及许多人类疾病的病理生理事件。凋亡信号调节激酶1 (ASK1)是一个上游靶点，仅在病理条件下被激活，因此是治疗干预的一个有希望的靶点。在这篇综述的第一部分，将描述导致ASK1激活和调控的分子机制，以及支持ASK1在人类疾病中的致病作用的证据。在第二部分中，将提供针对ask1靶向疗法的发现和开发的最新药物发现工作。

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Discovery and development of ASK1 inhibitors.

Aberrant activation of mitogen-activated protein kinases (MAPKs) like c-Jun N-terminal kinase (JNK) and p38 is an event involved in the pathophysiology of numerous human diseases. The apoptosis signal-regulating kinase 1 (ASK1) is an upstream target that gets activated only under pathological conditions and as such is a promising target for therapeutic intervention. In the first part of this review the molecular mechanisms leading to ASK1 activation and regulation will be described as well as the evidences supporting a pathogenic role for ASK1 in human disease. In the second part, an update on drug discovery efforts towards the discovery and development of ASK1-targeting therapies will be provided.

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来源期刊

Progress in medicinal chemistry Pharmacology, Toxicology and Pharmaceutics-Pharmacology

CiteScore

15.60

自引率

0.00%

发文量

期刊介绍： This series has a long established reputation for excellent coverage of almost every facet of Medicinal Chemistry and is one of the most respected and instructive sources of information on the subject. The latest volume certifies to the continuing success of a unique series reflecting current progress in a broadly developing field of science.