Ji, Suhyun Kim, Han Byeol Song, Yeonju Chung, Hwan Won Lee, Duck-Hyung Jung, Cheulhee Ko, Yeon jin Han, Seojung 2024-03-20T00:30:06Z 2024-03-20T00:30:06Z 2024-03-19 2024-04 0960-894X https://pubs.kist.re.kr/handle/201004/149490 Lymphocyte-specific protein tyrosine kinase (Lck) plays vital roles in the T-cell receptor- mediated development, function, and differentiation of T-cells. Given its substantial involvement in T cell signaling, irregularities in the expression and functionality of Lck may lead to various diseases, including cancer. In this study, we found that compound 12a exerted significant inhibitory potency against Lck with an IC50 value of 10.6 nM. In addition, 12a demonstrated high efficacy in various colon cancer cell lines as indicated by GI50 values ranging from 0.24 to 1.26 μM. Notably, 12a inhibited the phosphorylation of Lck in Colo201 cells. Overall, the anti-proliferative effects of 12a on diverse cancer cell lines highlights its potential application for the treatment of various cancer types. English Pergamon Press Ltd. Identification of 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one scaffolds as potent Lck inhibitors as anti-cancer agents Article 10.1016/j.bmcl.2024.129645 1 Bioorganic & Medicinal Chemistry Letters, v.102, no.1 Bioorganic & Medicinal Chemistry Letters 102 1 N scie scopus 001197791900001 Chemistry, Medicinal Chemistry, Organic Pharmacology & Pharmacy Chemistry Article TYROSINE KINASE DISCOVERY P56(LCK) EXPRESSION A-770041 PROMOTER COMPLEX SAR Lck Colon cancer Kinase Drug design Cancer