In Silico Studies of Novel Vemurafenib Derivatives as BRAF Kinase Inhibitors.

ABSTRACT: BRAF inhibitors have improved the treatment of advanced or metastatic melanoma in patients that harbor a BRAF^T1799A mutation. Because of new insights into the role of aberrant glycosylation in drug resistance, we designed and studied three novel vemurafenib derivatives possessing pentose-associated aliphatic ligands-methyl-, ethyl-, and isopropyl-ketopentose moieties-as potent BRAF_V600E kinase inhibitors. The geometries of these derivatives were optimized using the density functional theory method. Molecular dynamic simulations were performed to find interactions between the ligands and BRAF_V600E kinase. Virtual screening was performed to assess the fate of derivatives and their systemic toxicity, genotoxicity, and carcinogenicity. The computational mapping

SUBMITTER: Zolek T 

PROVIDER: S-EPMC10343629 | biostudies-literature | 2023 Jul

REPOSITORIES: biostudies-literature