肿瘤坏死因子（TNF）是一种多效细胞因子，在免疫系统稳态调节中起着重要作用，并参与许多炎症性和自身免疫性疾病的发生，如类风湿关节炎（RA）、牛皮癣、阿尔茨海默病（AD）和多发性硬化症（MS）。因此，TNF及其受体TNFR1和TNFR2是相关的药理靶点。生物制剂已被开发用于阻断TNF依赖的信号级联，但它们显示出严重的副作用，并且由于免疫原性，它们的药理效应随时间减少。在本综述中，我们介绍了针对TNF及其受体的小分子近期发现，并讨论调节TNF信号的替代策略。简介：本综述介绍了几种近期和创新的肿瘤坏死因子功能调节策略，重点关注小分子。 Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Tumor necrosis factor (TNF) is a pleiotropic cytokine with a major role in immune system homeostasis and is involved in many inflammatory and autoimmune diseases, such as rheumatoid arthritis (RA), psoriasis, Alzheimer's disease (AD), and multiple sclerosis (MS). Thus, TNF and its receptors, TNFR1 and TNFR2, are relevant pharmacological targets. Biologics have been developed to block TNF-dependent signaling cascades, but they display serious side effects, and their pharmacological effectiveness decreases over time because of their immunogenicity. In this review, we present recent discoveries in small molecules targeting TNF and its receptors and discuss alternative strategies for modulating TNF signaling. Teaser: This review presents several recent and innovative strategies for the modulation of tumor necrosis factor function, with a focus on small molecules.Copyright © 2023 The Author(s). Published by Elsevier Ltd.. All rights reserved.