Repurposing Drugs by In Silico Methods to Target BCR Kinase Domain in Chronic Myeloid Leukemia.

ABSTRACT: BACKGROUND:Targeted therapy in the form of highly selective tyrosine kinase inhibitors (TKIs) has transformed the treatment of chronic myeloid leukemia (CML). However, mutations in the kinase domain contribute to drug resistance against TKIs which compromises the treatment response. Our aim is to explore regions outside the BCR-ABL oncoprotein to identify potential therapeutic targets to curb drug resistance by targeting growth factor receptor-bound protein-2 (Grb-2) which binds to BCR-ABL at the phosphorylated tyrosine (Y177) thereby activating the Ras and PI3K/AKT signaling pathway. METHODS:We have used in silico methods to repurpose drugs for identifying their potential to inhibit the binding of Grb-2 with Y177 by occupying the active binding site of the BCR domain. RESULTS:Differential

SUBMITTER: Natarajan A 

PROVIDER: S-EPMC7063026 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature