About A public-private partnership that supports the discovery of new medicines through open access research. Mission and Philosophy Partners Governance Collaborators Laboratories Key Achievements Research Collaborations and Communications Why Companies Enter Open Science Partnerships with SGC SGC Open Science Policy Equity, Diversity and Inclusion FAQs Science TARGET ENABLING PACKAGES (TEPs) TISSUE PLATFORM PROTEIN STRUCTURES PUBLICATIONS CHEMICAL PROBES Donated chemical probes Biological probes Human Kinase Chemical Probe Program Probes against other protein classes RECOMBINANT ANTIBODIES Structure-guided Drug Discovery Coalition (SDDC) SDDC Publications CREATE ChemNET Research Program Trainees Open Access Learning Impact Faculty & Industry Participants Structural & Chemical Biology Bootcamp Events Structural Biology Programme Structural Parasitology Rare Diseases Genome Integrity and Neurodegeneration Growth Factor Signalling Integral Membrane Proteins Metabolic Enzymes Phosphorylation-Dependent Signalling Protein Kinases Ubiquitin Biology Chemical Biology Antibodies Protein Families Methyl Lysine Readers Histone Deacetylases Histone Acetyltransferases Demethylases Bromodomains Protein Methyltransferases Probe Development Screening Platforms Epigenetic Cell Assays Fragment Based Screening Informatics Medicinal Chemistry ChromoHub Phylogenetic Trees UbiHub Phylogenetic Trees Histone Tails Epigenetics Pocketome Technological Science Biotechnology Biophysics Screening Platforms Research Informatics Protein Crystallography Medicinal Chemistry Reagents & Resources Reagents Chemical Probes Antibodies SGC Vectors SGC Plasmids SGC Constructs Resources Structure Gallery Protein Production Protocols ChromoHub Phylogenetic Trees UbiHub Phylogenetic Trees Histone Tails Fragment Screening Crystal Forms Fragalysis MichaelaNGLo Technologies High Throughput Protein Crystallisation Lex Bubbling System Frapid People Global SGC Director Aled Edwards Susan McCormick Max Morgan Academic Collaborators Industrial/ SME collaborators Non-Scientists SGC OCN Mat Todd SGC Neuro Edward Fon Ziv Gan-Or Thomas Durcan Roxanne Lariviere Peter McPherson Jean-François Trempe Carl Laflamme Toronto Cheryl Arrowsmith Dalia Barsyte-Lovejoy Peter J. Brown Jinrong Min Takis Prinos Matthieu Schapira Masoud Vedadi Levon Halabelian Biotechnology Crystallography UNC Tim Willson Alison Axtman David Drewry Karolinska Michael Sundström Susanne Gräslund Louise Berg Per-Johan Jakobsson Frankfurt Stefan Knapp Susanne Müller-Knapp Apirat Chaikuad Thomas Hanke Vladimir Rogov Krishnal Saxena Andreas Joerger Václav Němec News & Outreach News & Events SGC News Symposia & Workshops Blog Press Releases Public Events Public Engagement SGC Languages General Public Open Lab Notebooks Schools Media Patient Groups Governments TOronto Ubiquitin Club And Network (TOUCAN) Careers Tweets by thesgconline
A public-private partnership that supports the discovery of new medicines through open access research.
SGC-UBD253 Chemical probe for the ubiquitin binding domain of HDAC6.The probe and control may be requested here. For any inquiries please contact proberequests@thesgc.org.group newOverviewSGC in collaboration with Dr Mark Lautens’ at the University of Toronto’s Department of Chemistry has developed the first chemical probe SGC-UBD253 for the ubiquitin binding domain (UBD) of HDAC6. SGC-UBD253 binds potently to HDAC6 UBD with KD = 84 nM (SPR) and inhibits the HDAC6-ISG15 interaction with EC50 = 1.9 micromolar (nanoBRET). SGC-UBD253N is a closely related negative control with KD = 32 micromolar (SPR). Selectivity ProfileUsing sequence alignment of Zf-UBD pocket, 10 UBD-containing proteins in addition to HDAC6 were purified and tested for direct binding by SPR. In Vitro Potency Three biophysical methods clearly show SGC-UBD253 potently (≤100 nM) binds HDAC6-UBD. Cell-based Assay DataUsing a nanoBRET assay, the chemical probe SGC-UBD253 considerably decreases the interaction between full-length HDAC6 with ISG15 relative to SGC-UBD253N. References Ferreira de Freitas R, Harding RJ, Franzoni I, Ravichandran M, Mann MK, Ouyang H, Lautens M, Santhakumar V, Arrowsmith CH, Schapira M. Identification and Structure-Activity Relationship of HDAC6 Zinc-Finger Ubiquitin Binding Domain Inhibitors. J Med Chem. 2018 May 24;61(10):4517-4527. doi: 10.1021/acs.jmedchem.8b00258. PMID: 29741882 Harding RJ, Ferreira de Freitas R, Collins P, Franzoni I, Ravichandran M, Ouyang H, Juarez-Ornelas KA, Lautens M, Schapira M, von Delft F, Santhakumar V, Arrowsmith CH. Small Molecule Antagonists of the Interaction between the Histone Deacetylase 6 Zinc-Finger Domain and Ubiquitin. J Med Chem. 2017 Nov 9;60(21):9090-9096. doi: 10.1021/acs.jmedchem.7b00933. PMID: 29019676