Synthesis of non-brain-permeant inhibitor of LZK

LZK非透脑抑制剂的合成

• 批准号: 10001308
• 负责人: Matthew Hall
• 金额: $ 13.27万
• 依托单位: NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES
• 依托单位国家: 美国
• 资助国家: 美国
• 起止时间: 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10001308
• 关键词: Animal Model; Animals; Brain; Chemicals; Collaborations; Disease; Extramural Activities; Genomics; Goals; Head and Neck Cancer; Informatics; Modeling; Mus; Pharmaceutical Chemistry; Phosphotransferases; Plasma; Process; Research; Testing; United States National Institutes of Health; Work; drug discovery; inhibitor/antagonist; kinase inhibitor; new therapeutic target; screening; small molecule; small molecule inhibitor; small molecule therapeutics; therapeutic development

LZK has been identified as a novel therapeutic target in head and neck cancer. This project aims to synthesize small molecule inhibitors of the LZK kinase that are non-brain permeant to enable proof-of-concept animal studies. During this period, the previously synthesized LZK inhibitors were tested in a PK mouse study, and they all still showed a high brain to plasma ratio. As such, a tolerability screen is now underway to examine whether these inhibitors are indeed toxic to mice. If not, then these compounds can still be used in advanced animal models.

LZK已被确定为头颈癌的新治疗靶点。该项目旨在合成非脑渗透的LZK激酶的小分子抑制剂，以实现概念验证动物研究。 在此期间，先前合成的LZK抑制剂在PK小鼠研究中进行了测试，并且它们仍然显示出高的脑血浆比。因此，目前正在进行耐受性筛选，以检查这些抑制剂是否确实对小鼠有毒。如果没有，那么这些化合物仍然可以用于高级动物模型。