Identification of 3,4-dihydropyrimido[4,5-d]pyrimidin-2(1H)-one scaffolds as potent Lck inhibitors as anti-cancer agents

Su Hyun Ji, Han Byeol Kim, Yeonju Song, Hwan Won Chung, Duck Hyung Lee, Cheulhee Jung, Yeonjin Ko, Seo Jung Han

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Article number129645
JournalBioorganic and Medicinal Chemistry Letters
Volume102
DOIs
Publication statusPublished - 2024 Apr 1

Bibliographical note

Publisher Copyright:
© 2024 Elsevier Ltd

Keywords

  • Cancer
  • Colon cancer
  • Drug design
  • Kinase
  • Lck

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Molecular Biology
  • Pharmaceutical Science
  • Drug Discovery
  • Clinical Biochemistry
  • Organic Chemistry

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