Department of Pharmaceutical and Medicinal Chemistry, Eberhard Karls University Tübingen, Tübingen, Germany.
Cluster of Excellence iFIT (EXC 2180) "Image-Guided and Functionally Instructed Tumor Therapies", University of Tuebingen, Germany.
Expert Opin Ther Pat. 2020 Jun;30(6):453-466. doi: 10.1080/13543776.2020.1749263. Epub 2020 Apr 20.
: During the first half of the last decade the p38 MAP kinase family was a very popular target in academic as well as industrial research programs. Many attempts to achieve marketing authorization for a p38 MAPK inhibitor for the treatment of pro-inflammatory diseases, like rheumatoid arthritis (RA), failed at the state of clinical trials, mostly due to selectivity and/or toxicity issues.: Herein, the patents and corresponding publications of international companies, universities and other research institutions, which focus on the development, identification and optimization of new selective p38 inhibitors and their fields of use are summarized.: p38 MAP kinase inhibitors are a mature field with many pre-clinically validated structural classes, more than 20 candidates in clinical trials but still (except the weak and unselective p38 inhibitor pirfenidone) no approved drug. Big Pharma hasn't contributed much to the patents of the last five years but remarkable contribution have come from academic environment or small biotech companies. Three general punchlines of innovation have shown up. Tailor-made molecules with properties for local application, mainly type-II (Urea-type) inhibitors for lung- or skin diseases, isoform p38γ,δ-selective inhibitors for the treatment of cutaneous t-cell lymphoma (CTCL) and substrate-specific inhibitors (e.g. p38/MK2).
在过去十年的前半段时间，p38 MAP 激酶家族一直是学术和工业研究计划中的一个非常热门的目标。许多试图为治疗炎症性疾病（如类风湿关节炎（RA））的 p38 MAPK 抑制剂获得营销授权的尝试都在临床试验阶段失败了，主要是由于选择性和/或毒性问题。
在此，总结了国际公司、大学和其他研究机构的专利和相关出版物，这些专利和出版物主要集中在开发、鉴定和优化新型选择性 p38 抑制剂及其用途上。
p38 MAP 激酶抑制剂是一个成熟的领域，有许多经过临床前验证的结构类别，有 20 多个候选药物在临床试验中，但仍（除了弱且非选择性的 p38 抑制剂吡非尼酮）没有批准的药物。大型制药公司在过去五年的专利方面贡献不大，但学术环境或小型生物技术公司做出了显著贡献。有三个创新的总体要点已经出现。具有局部应用特性的定制分子，主要是用于肺部或皮肤疾病的 II 型（尿素型）抑制剂、用于治疗皮肤 T 细胞淋巴瘤（CTCL）的 p38γ、δ 选择性抑制剂以及底物特异性抑制剂（例如 p38/MK2）。
