Covalent Modifiers

Discovery and Characterization of Divarasib (GDC-6036), a Potent Covalent Inhibitor of KRAS G12C https://covalentmodifiers.blogspot.com/2026/03/discovery-and-characterization-of.html

A Tandem Bioorthogonal Retro-Cope and Cope Elimination for the Activation of Covalent Inhibitors with an Acrylamide or Vinylsulfonamide Warhead in Live Cells https://covalentmodifiers.blogspot.com/2026/02/a-tandem-bioorthogonal-retro-cope-and.html

Discovery of a Potent, Selective, and In Vivo Efficacious Covalent Inhibitor for Lysine Methyltransferase SETD8 https://covalentmodifiers.blogspot.com/2026/02/discovery-of-potent-selective-and-in.html

Exploiting human fucosyltransferase 8 allostery with a covalent inhibitor for core fucosylation suppression https://covalentmodifiers.blogspot.com/2026/02/exploiting-human-fucosyltransferase-8.html

Covalent inhibitor design confers activity against both GDP- and GTP-bound forms of KRAS G12C https://covalentmodifiers.blogspot.com/2026/02/covalent-inhibitor-design-confers.html

Development of a Lysine-Reactive Targeted Covalent Inhibitor (TCI) for the P300/CBP-Associated Factor (PCAF) Bromodomain Through Structure-Based Design https://covalentmodifiers.blogspot.com/2026/02/development-of-lysine-reactive-targeted.html

Covalent Protein Inhibitors via Tyrosine and Tryptophan Conjugation with Cyclic Imine Mannich Electrophiles https://covalentmodifiers.blogspot.com/2026/02/covalent-protein-inhibitors-via.html

Chemoproteomics discovery of a CNS-penetrant covalent inhibitor of PIKfyve https://covalentmodifiers.blogspot.com/2026/02/chemoproteomics-discovery-of-cns.html

Group Competition Strategy for Covalent Ligand Discovery https://covalentmodifiers.blogspot.com/2026/01/group-competition-strategy-for-covalent.html

Protein tyrosine phosphatase inactivation by electrophilic tyrosine modification https://covalentmodifiers.blogspot.com/2026/01/protein-tyrosine-phosphatase.html

Covalent Peptide-Encoded Libraries Enable Discovery of Inhibitors of Epidermal Growth Factor Receptor (EGFR) https://covalentmodifiers.blogspot.com/2026/01/covalent-peptide-encoded-libraries.html

Structure-Guided Optimization of 4-Chloro-Pyrazolopyridine Analogs for Covalent PREP Inhibition https://covalentmodifiers.blogspot.com/2026/01/structure-guided-optimization-of-4.html

Ninhydrin as a covalent warhead for chemical proteomic-enabled discovery and selective engagement of reactive arginines https://covalentmodifiers.blogspot.com/2026/01/ninhydrin-as-covalent-warhead-for.html

Peptide-based covalent inhibitor of tubulin detyrosination promotes mesenchymal-to-epithelial transition in lung cancer cells https://covalentmodifiers.blogspot.com/2026/01/peptide-based-covalent-inhibitor-of.html

Discovery of a First-in-Class Covalent Allosteric SHP1 Inhibitor with Immunotherapeutic Activity https://covalentmodifiers.blogspot.com/2025/12/discovery-of-first-in-class-covalent.html

Covalent Drug Binding in Live Cells Monitored by Mid-Infrared Quantum Cascade Laser Spectroscopy: Photoactive Yellow Protein as a Model System https://covalentmodifiers.blogspot.com/2025/12/covalent-drug-binding-in-live-cells.html

A practical method for determining the rate of covalent modification of fragments and leads https://covalentmodifiers.blogspot.com/2025/12/a-practical-method-for-determining-rate.html

Stereoselective Degradation of Diacylglycerol Kinases Potentiate T cell Activation and Tumor Cell Cytotoxicity https://covalentmodifiers.blogspot.com/2025/12/stereoselective-degradation-of.html

Identification of VVD-214/RO7589831, a Clinical-Stage, Covalent Allosteric Inhibitor of WRN Helicase for the Treatment of MSI-High Cancers https://covalentmodifiers.blogspot.com/2025/12/identification-of-vvd-214ro7589831.html

The Development of UM-203, A Reversible Covalent STING Antagonis https://covalentmodifiers.blogspot.com/2025/12/the-development-of-um-203-reversible.html

A Highly Reactive Cysteine-Targeted Acrylophenone Chemical Probe That Enables Peptide/Protein Bioconjugation and Chemoproteomics Analysis https://covalentmodifiers.blogspot.com/2025/12/a-highly-reactive-cysteine-targeted.html

Preclinical characterization of EGT710, an oral non-peptidomimetic reversible covalent SARS-CoV-2 main protease inhibitor https://covalentmodifiers.blogspot.com/2025/11/preclinical-characterization-of-egt710.html

Fast and Site-Specific Covalent Targeting of Proteins by Arylfluorosulfate-Modified Aptamers https://covalentmodifiers.blogspot.com/2025/11/fast-and-site-specific-covalent.html

Reimagining Druggability using Chemoproteomic Platforms YouTube video by Drug Hunter

youtu.be/4dC23U9S2Vc?... @dannomura.bsky.social @drug-hunter.bsky.social

A multicenter, open-label, first-in-human study of TYRA-200 in advanced intrahepatic cholangiocarcinoma and other solid tumors with activating FGFR2 gene alterations (SURF201). https://covalentmodifiers.blogspot.com/2025/10/a-multicenter-open-label-first-in-human.html

Discovery of Fulzerasib (GFH925) for the Treatment of KRAS G12C-Mutated Solid Tumors https://covalentmodifiers.blogspot.com/2025/10/discovery-of-fulzerasib-gfh925-for.html

Discovery of an Internal Alkyne Warhead Scaffold for Irreversible hTG2 Inhibition https://covalentmodifiers.blogspot.com/2025/10/discovery-of-internal-alkyne-warhead.html

Covalent Probes Reveal Small-Molecule Binding Pockets in Structured RNA and Enable Bioactive Compound Design https://covalentmodifiers.blogspot.com/2025/10/covalent-probes-reveal-small-molecule.html

AI-assisted delivery of novel covalent WRN inhibitors from a non-covalent fragment screen https://covalentmodifiers.blogspot.com/2025/10/ai-assisted-delivery-of-novel-covalent.html

Sulfinyl Aziridines as Stereoselective Covalent Destabilizing Degraders of the Oncogenic Transcription Factor MYC https://covalentmodifiers.blogspot.com/2025/09/sulfinyl-aziridines-as-stereoselective.html