Novel thiazole derivatives incorporating phenyl sulphonyl moiety as potent BRAFV600E kinase inhibitors targeting melanoma
Afaf Y. Khormi, Thoraya A. Farghaly, Abrar Bayazeed, Youssef O. Al‐Ghamdi, Hanan Gaber Abdulwahab, Mohamed R. Shaaban
Abstract
= 16.5 ± 0.91 μM). Compounds 7b, 11a and 11c, 13a, and 17 were much more potent than dabrafenib against B-RAFV600E-mutated WM266.4 melanoma cells. Furthermore, compound 7b suppressed the phosphorylation of downstream ERK1/2 from WM266.4 cells. Also, the docking study revealed the proper orientation and well-fitting of the title compounds into the ATP binding site of B-RAFV600E kinase.
Topics & Concepts
MoietyDabrafenibIC50ThiazoleKinaseMelanomaDocking (animal)StereochemistryIn vitroChemistryBiochemistryCancer researchBiologyMedicineMetastatic melanomaNursingVemurafenibMelanoma and MAPK PathwaysComputational Drug Discovery MethodsProtein Degradation and Inhibitors