ABSTRACT

Introduction

Interleukin-17A (IL-17A) is a well-established pro-inflammatory cytokine, which plays a pivotal role in immune and autoimmune diseases including psoriasis, asthma, psoriatic arthritis, and rheumatoid arthritis. Three currently approved monoclonal antibodies (mAbs) are in clinical practice for the treatment of multiple immune diseases. However, the disadvantages of the mAbs, such as non-oral administration, poor tissue penetration, lacking blood-brain barrier penetration, often long half-life times, narrow its application. Thus, intensive research is performed to discover potent small molecules, peptides, and macrocycles targeting the IL-17A/IL-17 RA protein–protein interaction (PPI) to modulate immune responses as an attractive approach for immunotherapy.

Areas covered

Small molecules, macrocycles, and peptides targeting IL-17A/IL-17RA PPI from 2013 to 2021.

Expert opinion

The rapid increase in the identification of small-molecule inhibitors of IL-17 should translate into a supplement of current biotherapeutics with mAbs. Potential advantages of small molecules over mAbs show room for clinical treatment improvement and new indication areas . An increasing number of patents and articles are recently published on small-molecule immunomodulators (SMIMs). Two compounds from Lilly and Leo Pharma are currently investigated in early clinical trials, followed by a Dice molecule. The outcome of these trials will influence future development of IL-17 inhibitors for treatment of inflammation-related diseases.

中文翻译：

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IL-17A/IL-17RA 的小分子调节剂：专利审查 (2013-2021)

摘要

介绍

白细胞介素 17A (IL-17A) 是一种公认​​的促炎细胞因子，在牛皮癣、哮喘、银屑病关节炎和类风湿性关节炎等免疫和自身免疫性疾病中起着关键作用。目前批准的三种单克隆抗体 (mAb) 正在临床实践中用于治疗多种免疫疾病。然而，单克隆抗体非口服给药、组织穿透性差、缺乏血脑屏障穿透性、半衰期通常较长等缺点限制了其应用。因此，进行了深入的研究以发现靶向 IL-17A/IL-17 RA 蛋白-蛋白相互作用 (PPI) 的有效小分子、肽和大环化合物，以调节免疫反应作为一种有吸引力的免疫治疗方法。

涵盖的领域

2013 年至 2021 年靶向 IL-17A/IL-17RA PPI 的小分子、大环化合物和肽。

专家意见

IL-17 小分子抑制剂鉴定的快速增加应该转化为对当前生物治疗药物的补充。小分子相对于 mAb 的潜在优势显示了临床治疗改进和新适应症领域的空间。最近发表的关于小分子免疫调节剂 (SMIM) 的专利和文章数量越来越多。Lilly 和 Leo Pharma 的两种化合物目前正在早期临床试验中进行研究，随后是 Dice 分子。这些试验的结果将影响未来用于治疗炎症相关疾病的 IL-17 抑制剂的开发。