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 SGC Open Science Policy FAQs Sitemap Science TARGET ENABLING PACKAGES (TEPs) TISSUE PLATFORM PROTEIN STRUCTURES PUBLICATIONS CHEMICAL PROBES Donated chemical probes Biological probes Epigenetics Probes Collection 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 Toronto Cheryl Arrowsmith Dalia Barsyte-Lovejoy Peter J. Brown Jinrong Min Takis Prinos Matthieu Schapira Masoud Vedadi Levon Halabelian Biotechnology Crystallography SGC OCN Mat Todd UNC 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.
PFI-7 The probe and control can be requested by clicking here. For any inquiries please contact proberequests@thesgc.org.group newOverviewPfizer in collaboration with the SGC have developed PFI-7, a potent, cell active chemical probe for the E3 ligase GID4. PFI-7 binds potently to GID4 with KD = 0.08 μM (SPR) and displaces the known degron1 peptide in a NanoBRETTM assay with EC50 = 0.6 μM. PFI-7N is a closely related negative control with KD = 5 μM (SPR). Chemical probe/control pair We have further developed a handle PFI-E3H1 and a PEGylated analogue to show that the handle tolerates a substitution. These findings offers opportunities to synthesize proximity-inducing or degrader modalities2. In Vitro Potency [PFI-7] (μM) [PFI-7] (μM) Cell-based Assay DataA NanoBRET assay was used to show target engagement in cells. The interaction was between NanoLuc® tagged degrons and full-length GID4. Co-crystal structures Main features 1. PFI-7 bound to GID4 substrate-binding pocket 2. Structure overview 3. Overlap with substrate peptide References Cheng Dong, Heng Zhang, Li Li, Wolfram Tempel, Peter Loppnau & Jinrong Min. Molecular basis of GID4-mediated recognition of degrons for the Pro/N-end rule pathway. Nature Chemical Biology 14, 466-473 (2018). Aleša Bricelj, Christian Steinebach, Robert Kuchta, Michael Gütschow, and Izidor Sosič. E3 Ligase Ligands in Successful PROTACs: An Overview of Syntheses and Linker Attachment Points, https://doi.org/10.3389/fchem.2021.707317 ; Milka Kostic. Targeted Protein Degradation and Proximity-Based Pharmacology, https://doi.org/10.5281/zenodo.5534371 .
