An in silico approach towards acute myeloid leukemia (with FLT3-ITD mutation) therapy using HSP90 as target

Abstract

About 20% of cases of acute myeloid leukemia (AML) show an internal tandem duplication of the juxta-position membrane domain of the protein FLT3 which belongs to the family of ligand receptor tyrosine kinase. The disease shows correlation with leukocytosis and poor prognosis as well as.Hsp 90 Inhibitors dissociated FLT3-ITD from the Hsp 90 chaperone complex and hence targeting the Hsp 90 could serve as anti-FLT3ITD therapy, and that the chaperone Hsp 90 is involved closely with the oncogenic activation of FLT3.The inhibitors gave best results at binding site 400 in general. Coumermycin A1 showed the best result with binding energy of -8.1 kcal/mol at the binding site 138 of the Hsp 90.Clorobiocin was yet another compound that showed promising results with energy value of -7.2 kcal/mol at binding site 400.Novobiocin was showed good results and is one of the most important used inhibitor in clinical trials currently in use.