We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Repurposing Synthetic Congeners of a Natural Product Aurone Unveils a Lead Antitumor Agent Inhibiting Folded P-Loop Conformation of MET Receptor Tyrosine Kinase.
- Authors
Hassan, Ahmed H. E.; Wang, Cai Yi; Lee, Cheol Jung; Jeon, Hye Rim; Choi, Yeonwoo; Moon, Suyeon; Lee, Chae Hyeon; Kim, Yeon Ju; Cho, Soo Bin; Mahmoud, Kazem; El-Sayed, Selwan M.; Lee, Sang Kook; Lee, Yong Sup
- Abstract
A library of 24 congeners of the natural product sulfuretin were evaluated against nine panels representing nine cancer diseases. While sulfuretin elicited very weak activities at 10 µM concentration, congener 1t was identified as a potential compound triggering growth inhibition of diverse cell lines. Mechanistic studies in HCT116 colon cancer cells revealed that congener 1t dose-dependently increased levels of cleaved-caspases 8 and 9 and cleaved-PARP, while it concentration-dependently decreased levels of CDK4, CDK6, Cdc25A, and Cyclin D and E resulting in induction of cell cycle arrest and apoptosis in colon cancer HCT116 cells. Mechanistic study also presented MET receptor tyrosine kinase as the molecular target mediating the anticancer activity of compound 1t in HCT116 cells. In silico study predicted folded p-loop conformation as the form of MET receptor tyrosine kinase responsible for binding of compound 1t. Together, the current study presents compound 1t as an interesting anticancer lead for further development.
- Subjects
MET receptor; NATURAL products; ANTINEOPLASTIC agents; COLON cancer; CELL cycle
- Publication
Pharmaceuticals (14248247), 2023, Vol 16, Issue 11, p1597
- ISSN
1424-8247
- Publication type
Article
- DOI
10.3390/ph16111597