title: From determinants of RUNX1/ETO tetramerization to small-molecule protein-protein interaction inhibitors targeting acute myeloid leukemia.
abstract: We identified the first small-molecule protein-protein interaction inhibitors of RUNX1/ETO tetramerization applying structure-based virtual screening guided by predicted hot spots and pockets in the interface. A 3D similarity screening revealed specific hot spot mimetics, one of which prevents the proliferation of RUNX1/ETO-dependent SKNO-1 cells at low micromolar concentration. Using solely a protein-protein complex structure to start with, this strategy can be the first step in any comparable structure-based endeavor to identify protein-protein interaction inhibitors.
authors: Institute for Pharmaceutical and Medicinal Chemistry, Department of Mathematics and Natural Sciences, Heinrich-Heine-University , Universitätsstr. 1, 40225 Düsseldorf, Germany.
authors: Alexander
authors: A
authors: Metz
authors: Julia
authors: J
authors: Schanda
authors: Manuel
authors: M
authors: Grez
authors: Christian
authors: C
authors: Wichmann
authors: Holger
authors: H
authors: Gohlke
mesh_terms: D045744:Cell Line, Tumor; D049109:Cell Proliferation; D050676:Core Binding Factor Alpha 2 Subunit / Q000737:chemistry*; D006801:Humans; D007951:Leukemia, Myeloid / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D008958:Models, Molecular; D058990:Molecular Targeted Therapy; D011485:Protein Binding / Q000187:drug effects; D055503:Protein Multimerization / Q000187:drug effects*; D020836:Protein Structure, Quaternary; D011518:Proto-Oncogene Proteins / Q000737:chemistry*; D000075142:RUNX1 Translocation Partner 1 Protein; D054852:Small Molecule Libraries / Q000494:pharmacology*; D014157:Transcription Factors / Q000737:chemistry*
chemical_list: D050676:Core Binding Factor Alpha 2 Subunit; D011518:Proto-Oncogene Proteins; D000075142:RUNX1 Translocation Partner 1 Protein; C082222:RUNX1T1 protein, human; D054852:Small Molecule Libraries; D014157:Transcription Factors