Structure-guided discovery and characterization of novel FLT3 inhibitors for acute myeloid leukemia treatment.

ABSTRACT: FLT3 (FMS-like tyrosine kinase 3), a receptor tyrosine kinase, is frequently mutated in acute myeloid leukemia (AML), a hematologic malignancy marked by aggressive proliferation, poor prognosis, and high relapse rates. Although FDA-approved FLT3 inhibitors exist, their clinical efficacy is often undermined by resistance and off-target effects, underscoring the critical necessity for more effective and selective agents. Here, we employed a structure-based computational approach combining pharmacophore screening via Pharmit and the MolPort compound library to identify novel FLT3 inhibitors. Pharmacophore modeling, virtual screening, and docking identified two promising leads, MolPort-002-705-878 and MolPort-007-550-904, with binding affinities of -11.33 and -10.66 kcal/mol, correspondingly.

SUBMITTER: Budha B 

PROVIDER: S-EPMC12517515 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature