化学
正电子发射断层摄影术
酪氨酸激酶
体内
Pet成像
冲刷
帕金森病
神经保护
药理学
核医学
受体
生物化学
疾病
医学
病理
内科学
生物技术
生物
作者
E. Johanna L. Stéen,A Yeong Park,Wissam Beaino,Changdev G. Gadhe,Esther Kooijman,Robert C. Schuit,Maxime Schreurs,Prisca Leferink,Jeroen J. M. Hoozemans,Jae Eun Kim,Jinhwa Lee,Albert D. Windhorst
标识
DOI:10.1021/acs.jmedchem.3c00902
摘要
Activated Abelson non-receptor tyrosine kinase (c-Abl) plays a harmful role in neurodegenerative conditions such as Parkinson's disease (PD). Inhibition of c-Abl is reported to have a neuroprotective effect and be a promising therapeutic strategy for PD. We have previously identified a series of benzo[d]thiazole derivatives as selective c-Abl inhibitors from which one compound showed high therapeutic potential. Herein, we report the development of a complementary positron emission tomography (PET) tracer. In total, three PET tracer candidates were developed and eventually radiolabeled with fluorine-18 for in vivo evaluation studies in mice. Candidate [18F]3 was identified as the most promising compound, since it showed sufficient brain uptake, good washout kinetics, and satisfactory metabolic stability. In conclusion, we believe this tracer provides a good starting point to further validate and explore c-Abl as a target for therapeutic strategies against PD supported by PET.
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