Targeting cyclin-dependent kinases in rheumatoid arthritis and psoriasis - a review of current evidence.

IF 4.6 2区 医学 Q1 PHARMACOLOGY & PHARMACY
Expert Opinion on Therapeutic Targets Pub Date : 2023-07-01 Epub Date: 2023-12-07 DOI:10.1080/14728222.2023.2285784
Marzena Staniszewska, Kajetan Kiełbowski, Klaudia Rusińska, Estera Bakinowska, Ewa Gromowska, Andrzej Pawlik
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引用次数: 0

Abstract

Introduction: Rheumatoid arthritis (RA) is a chronic inflammatory disease associated with synovial proliferation and bone erosion, which leads to the structural and functional impairment of the joints. Immune cells, together with synoviocytes, induce a pro-inflammatory environment and novel treatment agents target inflammatory cytokines. Psoriasis is a chronic immune-mediated skin disease, and several cytokines are considered as typical mediators in the progression of the disease, including IL-23, IL-22, and IL-17, among others.

Area covered: In this review, we try to evaluate whether cyclin-dependent kinases (CDK), enzymes that regulate cell cycle and transcription of various genes, could become novel therapeutic targets in RA and psoriasis. We present the main results of in vitro and in vivo studies, as well as scarce clinical reports.

Expert opinion: CDK inhibitors seem promising for treating RA and psoriasis because of their multidirectional effects. CDK inhibitors may affect not only the process of osteoclastogenesis, thereby reducing joint destruction in RA, but also the process of apoptosis of neutrophils and macrophages responsible for the development of inflammation in both RA and psoriasis. However, assessing the efficacy of these drugs in clinical practice requires multi-center, long-term clinical trials evaluating the effectiveness and safety of CDK-blocking therapy in RA and psoriasis.

靶向周期蛋白依赖性激酶治疗类风湿性关节炎和牛皮癣-当前证据综述
类风湿关节炎(RA)是一种与滑膜增生和骨侵蚀相关的慢性炎症性疾病,可导致关节的结构和功能损害。免疫细胞与滑膜细胞一起诱导促炎环境和新的治疗药物靶向炎症细胞因子。银屑病是一种慢性免疫介导的皮肤病,几种细胞因子被认为是疾病进展的典型介质,包括IL-23、IL-22和IL-17等。涉及领域:在这篇综述中,我们试图评估细胞周期蛋白依赖性激酶(CDK),一种调节细胞周期和各种基因转录的酶,是否可以成为RA和牛皮癣的新治疗靶点。我们提出了体外和体内研究的主要结果,以及稀缺的临床报告。专家意见:由于CDK抑制剂的多向作用,治疗类风湿性关节炎和牛皮癣似乎很有希望。CDK抑制剂可能不仅影响破骨细胞生成过程,从而减少RA的关节破坏,而且还影响中性粒细胞和巨噬细胞的凋亡过程,这些中性粒细胞和巨噬细胞在RA和牛皮癣中都是炎症的发生。然而,在临床实践中评估这些药物的疗效需要多中心、长期的临床试验来评估cdk阻断治疗RA和牛皮癣的有效性和安全性。
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来源期刊
CiteScore
8.90
自引率
1.70%
发文量
58
审稿时长
3 months
期刊介绍: The journal evaluates molecules, signalling pathways, receptors and other therapeutic targets and their potential as candidates for drug development. Articles in this journal focus on the molecular level and early preclinical studies. Articles should not include clinical information including specific drugs and clinical trials. The Editors welcome: Reviews covering novel disease targets at the molecular level and information on early preclinical studies and their implications for future drug development. Articles should not include clinical information including specific drugs and clinical trials. Original research papers reporting results of target selection and validation studies and basic mechanism of action studies for investigative and marketed drugs. The audience consists of scientists, managers and decision makers in the pharmaceutical industry, academic researchers working in the field of molecular medicine and others closely involved in R&D.
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