Heriot-Watt University, Edinburgh, UK.
Expert Opin Ther Pat. 2010 Apr;20(4):471-95. doi: 10.1517/13543771003639436.
JAK2 is one of the most promising targets against neoplastic growth. A somatic mutation (V617F) resulting in enhanced JAK2 kinase activity can be frequently found in patients with serious myeloproliferative neoplasms such as polycythemia vera, essential thrombocythemia and primary myelofibrosis. Preclinical results strongly support that JAK2 inhibitors could be effectively used in these indications. Pharmaceutical companies and academic groups have developed a number of potent JAK2 inhibitors during the last decade. Tolerability and effectiveness of the most promising compounds are currently being investigated in clinical trials.
In this paper, we aim to give a comprehensive review of the currently available patent literature of JAK2 inhibitors.
We tried to collect the published core structures possessing JAK2 inhibitory potency including compounds developed by academic and industrial research groups. We review the currently available patent literature as well as the key papers containing additional information about the described JAK2 inhibitors. Clinical status data were collected by searching the Prous Integrity and Pharmaprojects databases.
The significant number of JAK2 inhibitors published and numerous clinical trials involving these compounds suggest that some of them might be approved in the next few years and can serve as novel drugs for the treatment of JAK2-dependent pathologies.
JAK2 是针对肿瘤生长最有前途的目标之一。体细胞突变（V617F）导致增强的 JAK2 激酶活性，可在严重的骨髓增生性肿瘤患者中经常发现，如真性红细胞增多症，原发性血小板增多症和原发性骨髓纤维化。临床前结果强烈支持 JAK2 抑制剂可在这些适应症中有效使用。制药公司和学术团体在过去十年中开发了许多有效的 JAK2 抑制剂。目前正在临床试验中研究最有前途的化合物的耐受性和有效性。
在本文中，我们旨在对目前可获得的 JAK2 抑制剂专利文献进行全面综述。
我们试图收集具有 JAK2 抑制活性的已发表的核心结构，包括学术和工业研究小组开发的化合物。我们综述了目前可获得的专利文献以及包含描述的 JAK2 抑制剂的其他信息的关键论文。通过搜索 Prous 完整性和 Pharmaprojects 数据库收集临床状态数据。
大量已发表的 JAK2 抑制剂和涉及这些化合物的众多临床试验表明，其中一些可能在未来几年内获得批准，并可作为治疗 JAK2 依赖性疾病的新型药物。
