8-环丙基-2-(吡啶-3-基)噻唑并[5,4-]喹唑啉-9(8)-酮的生物学特性，一种有前景的双重特异性酪氨酸激酶1A（DYRK1A）抑制剂

Biological Characterization of 8-Cyclopropyl-2-(pyridin-3-yl)thiazolo[5,4-]quinazolin-9(8)-one, a Promising Inhibitor of DYRK1A.

作者信息

Fruit Corinne, Couly Florence, Bhansali Rahul, Rammohan Malini, Lindberg Mattias F, Crispino John D, Meijer Laurent, Besson Thierry

机构信息

Normandie Univ, UNIROUEN, INSA Rouen, CNRS, COBRA UMR 6014, 76000 Rouen, France.

Department of Medicine, Division of Hematology/Oncology, Northwestern University, Chicago, IL 60611, USA.

出版信息

Pharmaceuticals (Basel). 2019 Dec 17;12(4):185. doi: 10.3390/ph12040185.

DOI:10.3390/ph12040185

PMID:31861110

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6958357/

Abstract

Dual-specificity tyrosine phosphorylation-regulated kinases (DYRKs) hyperactivity has been linked to the development of a number of human malignancies. DYRK1A is the most studied family member, and the discovery of novel specific inhibitors is attracting considerable interest. The 8-cyclopropyl-2(pyridin-3-yl)thiazolo[5,4-]quinazolin-9(8)-one (also called ) was found to be a promising inhibitor of DYRK1A and was characterized in biological experiments, by western transfer and flow cytometry on SH-SY5Y and pre-B cells. Here, the results obtained with are compared to well-characterized known DYRK1A inhibitors (e.g., Leucettine and ).

摘要

双特异性酪氨酸磷酸化调节激酶（DYRKs）的过度活跃与多种人类恶性肿瘤的发生有关。DYRK1A是研究最多的家族成员，新型特异性抑制剂的发现引起了广泛关注。8-环丙基-2-（吡啶-3-基）噻唑并[5,4-]喹唑啉-9（8H）-酮（也称为）被发现是一种有前景的DYRK1A抑制剂，并在生物学实验中通过蛋白质免疫印迹以及对SH-SY5Y细胞和前B细胞进行流式细胞术分析进行了表征。在此，将使用获得的结果与特征明确的已知DYRK1A抑制剂（例如，亮抑酶肽和）的结果进行比较。