Covalent Modifiers

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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

Covalent Ligand Electrophiles Are Differentially Activated by Proximity Effects Which Govern Latent Protein Reactivit https://covalentmodifiers.blogspot.com/2025/09/covalent-ligand-electrophiles-are.html

A covalent inhibitor targeting Cys16 on RhoA in colorectal cancer https://covalentmodifiers.blogspot.com/2025/09/a-covalent-inhibitor-targeting-cys16-on.html

Covalent Irreversible Inhibitors of Tetracycline Destructases https://covalentmodifiers.blogspot.com/2025/09/covalent-irreversible-inhibitors-of.html

Covalent chemical probes https://covalentmodifiers.blogspot.com/2025/09/covalent-chemical-probes.html

Cell-Active, Irreversible Covalent Inhibitors Targeting a Surface-Exposed Non-Catalytic Lysine on Aurora a Kinase by Using Squarate Chemistry https://covalentmodifiers.blogspot.com/2025/09/cell-active-irreversible-covalent.html

Small-Molecule Covalent Stabilization and Inhibition of the TEAD·YAP1 Transcription Factor in Cancer Cells https://covalentmodifiers.blogspot.com/2025/08/small-molecule-covalent-stabilization.html

Chemoselective Installation of Electrophilic Warheads onto C-Terminal Peptide Hydrazides for Covalent Protease Inhibitor Synthesis https://covalentmodifiers.blogspot.com/2025/08/chemoselective-installation-of.html

Structure-based rational design of covalent probes https://covalentmodifiers.blogspot.com/2025/08/structure-based-rational-design-of.html

Potent Inducers of Paraptosis through Electronic Tuning of Hemicyanine Electrophiles https://covalentmodifiers.blogspot.com/2025/08/potent-inducers-of-paraptosis-through.html

Profiling the proteome-wide selectivity of diverse electrophiles https://covalentmodifiers.blogspot.com/2025/08/profiling-proteome-wide-selectivity-of.html

Discovery of an Orally Bioavailable Reversible Covalent SARS-CoV-2 Mpro Inhibitor with Pan-Coronavirus Activity https://covalentmodifiers.blogspot.com/2025/08/discovery-of-orally-bioavailable.html

A twist in the tale: shifting from covalent targeting of a tyrosine in JAK3 to a lysine in MK2 https://covalentmodifiers.blogspot.com/2025/08/a-twist-in-tale-shifting-from-covalent.html

AGPAT4 targeted covalent inhibitor potentiates targeted therapy to overcome cancer cell plasticity in hepatocellular carcinoma mouse models https://covalentmodifiers.blogspot.com/2025/08/agpat4-targeted-covalent-inhibitor.html

A Covalent Self-Reporting Peptide Degrader Enables Real-Time Monitoring of Targeted Protein Degradation In Vivo https://covalentmodifiers.blogspot.com/2025/08/a-covalent-self-reporting-peptide.html

Research progress on covalent inhibitors targeting alkaline amino acids https://covalentmodifiers.blogspot.com/2025/07/research-progress-on-covalent.html

Orelabrutinib, an irreversible inhibitor of Bruton’s tyrosine kinase, for the treatment of systemic lupus erythematosus: a randomised, double-blind, placebo-controlled, phase Ib/IIa study https://covalentmodifiers.blogspot.com/2025/07/orelabrutinib-irreversible-inhibitor-of.html

State-of-the-art covalent virtual screening with AlphaFold3 https://covalentmodifiers.blogspot.com/2025/07/state-of-art-covalent-virtual-screening.html

The structure of KRASG12C bound to divarasib highlights features of potent switch-II pocket engagement https://covalentmodifiers.blogspot.com/2025/07/the-structure-of-krasg12c-bound-to.html

Rational Design of CDK12/13 and BRD4 Molecular Glue Degraders https://covalentmodifiers.blogspot.com/2025/07/rational-design-of-cdk1213-and-brd4.html

Discovery of the Clinical Candidate S-892216: A Second-Generation of SARS-CoV-2 3CL Protease Inhibitor for Treating COVID-19 https://covalentmodifiers.blogspot.com/2025/07/discovery-of-clinical-candidate-s.html

Diffusion Limit and the Reactivity/Affinity Conundrum: Implications for Optimization and Hit Finding for Irreversible Modulators https://covalentmodifiers.blogspot.com/2025/06/diffusion-limit-and-reactivityaffinity.html

Diethenyl Sulfoximine (DESI) as an Irreversible Lysine-Targeting Warhead Enables the Design of Covalent Allosteric EGFR Inhibitor https://covalentmodifiers.blogspot.com/2025/06/diethenyl-sulfoximine-desi-as.html

Introduction of Reactive Thiol Handles into Tyrosine-Tagged Proteins through Enzymatic Oxidative Coupling https://covalentmodifiers.blogspot.com/2025/06/introduction-of-reactive-thiol-handles.html