Aliashrafzadeh Hassan, Liu Dewey, De Alba Samantha, Akbar Imad, Lui Austin, Vanleuven Jordan, Martin Ryan, Wang Zhang, Liu Da Zhi
Department of Neurology, University of California, Davis, CA 95616, USA.
Ayub Medical College, Abbottabad 22020, Pakistan.
Explor Drug Sci. 2025;3. doi: 10.37349/eds.2025.1008116. Epub 2025 Jul 1.
Since our previous summary of the 74 FDA-approved kinase inhibitors in clinical and preclinical trials for non-cancerous neurological treatment, the US FDA has approved 13 additional kinase inhibitors since early 2022. This update incorporates new evidence for the now 87 FDA-approved kinase inhibitors in clinical and preclinical trials for the treatment of non-cancerous neurological disorders. By the end of October 2024, nearly all 87 FDA-approved kinase inhibitors have been tested in various animal models of non-cancerous neurological disorders, with twenty entered into clinical trials and six used for off-label treatments of neurological conditions in humans. Considering the challenges posed by intellectual property (IP), legal considerations, and limited blood-brain barrier (BBB) permeability, which may restrict some FDA-approved kinase inhibitors from effectively targeting the central nervous system (CNS), we further discuss the feasibility of designing novel proprietary analogs with enhanced BBB penetration to improve their therapeutic potential in neurological disorders. The new drugs typically retain full IP rights and remain costly; while repurposing kinase inhibitors may provide effective and affordable treatments for non-cancerous neurological disorders.
自从我们上次总结了74种经美国食品药品监督管理局(FDA)批准用于非癌性神经疾病临床和临床前试验的激酶抑制剂以来,自2022年初起,美国FDA又批准了13种激酶抑制剂。此次更新纳入了新的证据,涉及目前87种经FDA批准用于非癌性神经疾病临床和临床前试验的激酶抑制剂。到2024年10月底,几乎所有87种经FDA批准的激酶抑制剂都已在各种非癌性神经疾病动物模型中进行了测试,其中20种已进入临床试验,6种用于人类神经疾病的非标签治疗。考虑到知识产权(IP)、法律因素以及血脑屏障(BBB)通透性有限所带来的挑战,这些因素可能会限制一些经FDA批准的激酶抑制剂有效靶向中枢神经系统(CNS),我们进一步讨论了设计具有增强BBB通透性的新型专利类似物以提高其在神经疾病治疗潜力的可行性。新药通常保留完整的知识产权且成本高昂;而激酶抑制剂的重新利用可能为非癌性神经疾病提供有效且经济实惠的治疗方法。