Gilbert Adam M
Pharm Pat Anal. 2014 Jul;3(4):375-86. doi: 10.4155/ppa.14.24.
Despite concerns of off-target selectivity and cytotoxicity, there has been a resurgence in interest in irreversible kinase inhibitors resulting in more than 60 disclosed patent and patent applications over the past 4 years. Many of these inhibitors possess several key advantages over their reversible counterparts. The patent literature from 2010 to 2013 has been reviewed and novel irreversible kinase inhibitors for Bruton's tyrosine kinase, epidermal growth factor receptor, Janus kinase 3, phosphoinsitide 3 and other kinases are disclosed and discussed. These inhibitors offer novel treatments for mantle cell lymphoma, non-small-cell lung cancer, autoimmune disorders and severe metastatic cancers. A future perspective is presented on the likelihood of clinical success of these agents as well as the potential for new uses of irreversible kinase inhibitors in the future.
尽管存在脱靶选择性和细胞毒性方面的担忧,但过去四年中,不可逆激酶抑制剂重新引起了人们的兴趣,已有60多项公开的专利和专利申请。与可逆性激酶抑制剂相比,这些抑制剂中的许多都具有几个关键优势。对2010年至2013年的专利文献进行了综述,公开并讨论了用于布鲁顿酪氨酸激酶、表皮生长因子受体、Janus激酶3、磷脂酰肌醇-3激酶及其他激酶的新型不可逆激酶抑制剂。这些抑制剂为套细胞淋巴瘤、非小细胞肺癌、自身免疫性疾病和严重转移性癌症提供了新的治疗方法。文中还展望了这些药物临床成功的可能性以及未来不可逆激酶抑制剂新用途的潜力。