Chiral Analogues of PFI-1 as BET Inhibitors and Their Functional Role in Myeloid Malignancies
Bianca Altenburg, Marcus Frings, Jan‐Hendrik Schöbel, Jonas Goßen, Kristina Pannen, Kim Vanderliek, Giulia Rossetti, Steffen Koschmieder, Nicolas Chatain, Carsten Bolm
Abstract
Structural analogues of PFI-1 varying at the sulfur core were prepared, and their activities as BET inhibitors in myeloid cell lines and primary cells from patients with acute myeloid leukemia were studied. Docking calculations followed by molecular dynamics simulations revealed the binding mode of the newly prepared inhibitors, suggesting explanations for the observed high enantiospecificity of the inhibitory activity.
Topics & Concepts
Myeloid leukemiaDocking (animal)MyeloidCancer researchMyeloid cellsChemistryEnzymeStereochemistryBiochemistryComputational biologyPharmacologyMedicineBiologyNursingProtein Degradation and InhibitorsHistone Deacetylase Inhibitors ResearchHIV/AIDS drug development and treatment