A Perspective on the Kinetics of Covalent and Irreversible Inhibition

Recent progress on third generation covalent EGFR inhibitors

(2016) Hengmiao Cheng et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Positive Allosteric Modulation of the Glucagon-like Peptide-1 Receptor by Diverse Electrophiles

(2016) Ana B. Bueno et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of 1-{(3R,4R)-3-[({5-Chloro-2-[(1-methyl-1H-pyrazol-4-yl)amino]-7H-pyrrolo[2,3-d]pyrimidin-4-yl}oxy)methyl]-4-methoxypyrrolidin-1-yl}prop-2-en-1-one (PF-06459988), a Potent, WT Sparing, Irreversible Inhibitor of T790M-Containing EGFR Mutants

(2016) Hengmiao Cheng et al.   JOURNAL OF MEDICINAL CHEMISTRY

Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State

(2016) M. P. Patricelli et al.   Cancer Discovery

An algebraic model for the kinetics of covalent enzyme inhibition at low substrate concentrations

(2015) Petr Kuzmič et al.   ANALYTICAL BIOCHEMISTRY

Rapid Determination of the Specificity Constant of Irreversible Inhibitors (kinact/KI) by Means of an Endpoint Competition Assay

(2015) Ikuo Miyahisa et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Designing Irreversible Inhibitors-Worth the Effort?

(2015) Concepción González-Bello   ChemMedChem

Covalent inhibitors in drug discovery: from accidental discoveries to avoided liabilities and designed therapies

(2015) Renato A. Bauer   DRUG DISCOVERY TODAY

PAINS in the Assay: Chemical Mechanisms of Assay Interference and Promiscuous Enzymatic Inhibition Observed during a Sulfhydryl-Scavenging HTS

(2015) Jayme L. Dahlin et al.   JOURNAL OF MEDICINAL CHEMISTRY

An Aggregation Advisor for Ligand Discovery

(2015) John J. Irwin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Prolonged and tunable residence time using reversible covalent kinase inhibitors

(2015) J Michael Bradshaw et al.   Nature Chemical Biology

The promise and peril of chemical probes

(2015) Cheryl H Arrowsmith et al.   Nature Chemical Biology

Applying thermodynamic profiling in lead finding and optimization

(2015) Gerhard Klebe   NATURE REVIEWS DRUG DISCOVERY

Cancer epigenetics drug discovery and development: the challenge of hitting the mark

(2014) Robert M. Campbell et al.   JOURNAL OF CLINICAL INVESTIGATION

Chemical and Computational Methods for the Characterization of Covalent Reactive Groups for the Prospective Design of Irreversible Inhibitors

(2014) Mark E. Flanagan et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Fragment-Based Method to Discover Irreversible Covalent Inhibitors of Cysteine Proteases

(2014) Stefan G. Kathman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Promiscuity and Selectivity in Covalent Enzyme Inhibition: A Systematic Study of Electrophilic Fragments

(2014) Christian Jöst et al.   JOURNAL OF MEDICINAL CHEMISTRY

Chemistry: Chemical con artists foil drug discovery

(2014) Jonathan Baell et al.   NATURE

A road map to evaluate the proteome-wide selectivity of covalent kinase inhibitors

(2014) Bryan R Lanning et al.   Nature Chemical Biology

In vitro studies on the reaction rates of acrylamide with the key body-fluid thiols l-cysteine, glutathione, and captopril

(2014) Grace-Anne Bent et al.   Toxicology Research

What is the total number of protein molecules per cell volume? A call to rethink some published values

(2013) Ron Milo   BIOESSAYS

Learning from our mistakes: The ‘unknown knowns’ in fragment screening

(2013) Ben J. Davis et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Drug discovery considerations in the development of covalent inhibitors

(2013) Robert Mah et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Modification and Functional Inhibition of Regulator of G-Protein Signaling 4 (RGS4) by 4-Hydroxy-2-nonenal

(2013) C. Aaron Monroy et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Developing Irreversible Inhibitors of the Protein Kinase Cysteinome

(2013) Qingsong Liu et al.   CHEMISTRY & BIOLOGY

Redox regulation of protein kinases

(2013) Thu H. Truong et al.   CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY

Redox regulation of protein kinases

(2013) Aoife Corcoran et al.   FEBS Journal

Covalent EGFR inhibitor analysis reveals importance of reversible interactions to potency and mechanisms of drug resistance

(2013) P. A. Schwartz et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Monitoring Drug Target Engagement in Cells and Tissues Using the Cellular Thermal Shift Assay

(2013) D. M. Molina et al.   SCIENCE

Diverse Functional Roles of Reactive Cysteines

(2012) Nicholas J. Pace et al.   ACS Chemical Biology

Kinetic Template-Guided Tethering of Fragments

(2012) Rebecca H. Nonoo et al.   ChemMedChem

Drug discovery for a new generation of covalent drugs

(2012) Amit S Kalgutkar et al.   Expert Opinion on Drug Discovery

Bruton Tyrosine Kinase Inhibitor Ibrutinib (PCI-32765) Has Significant Activity in Patients With Relapsed/Refractory B-Cell Malignancies

(2012) Ranjana H. Advani et al.   JOURNAL OF CLINICAL ONCOLOGY

Discovery and Structure–Activity Relationship of Potent and Selective Covalent Inhibitors of Transglutaminase 2 for Huntington’s Disease

(2012) Michael E. Prime et al.   JOURNAL OF MEDICINAL CHEMISTRY

Covalent Inhibitors of Interleukin-2 Inducible T Cell Kinase (Itk) with Nanomolar Potency in a Whole-Blood Assay

(2012) Christoph W. Zapf et al.   JOURNAL OF MEDICINAL CHEMISTRY

Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles

(2012) Iana M Serafimova et al.   Nature Chemical Biology

On the Mechanism of Action of SJ-172550 in Inhibiting the Interaction of MDM4 and p53

(2012) Michal Bista et al.   PLoS One

Discovery of Brain-Penetrant, Irreversible Kynurenine Aminotransferase II Inhibitors for Schizophrenia

(2012) Amy B. Dounay et al.   ACS Medicinal Chemistry Letters

CYP3A Time-Dependent Inhibition Risk Assessment Validated with 400 Reference Drugs

(2011) A. Zimmerlin et al.   DRUG METABOLISM AND DISPOSITION

A Refined Cytochrome P450 IC50 Shift Assay for Reliably Identifying CYP3A Time-Dependent Inhibitors

(2011) P. Li et al.   DRUG METABOLISM AND DISPOSITION

Switching Reversibility to Irreversibility in Glycogen Synthase Kinase 3 Inhibitors: Clues for Specific Design of New Compounds

(2011) Daniel I. Perez et al.   JOURNAL OF MEDICINAL CHEMISTRY

Peroxide-dependent sulfenylation of the EGFR catalytic site enhances kinase activity

(2011) Candice E Paulsen et al.   Nature Chemical Biology

The resurgence of covalent drugs

(2011) Juswinder Singh et al.   NATURE REVIEWS DRUG DISCOVERY

SnapShot: Key Numbers in Biology

(2010) Uri Moran et al.   CELL

Characterization of Irreversible Kinase Inhibitors by Directly Detecting Covalent Bond Formation: A Tool for Dissecting Kinase Drug Resistance

(2010) Sabine Klüter  et al.   CHEMBIOCHEM

Redox cycling compounds generate H2O2 in HTS buffers containing strong reducing reagents—real hits or promiscuous artifacts?

(2010) Paul A Johnston   CURRENT OPINION IN CHEMICAL BIOLOGY

Strategies for discovering and derisking covalent, irreversible enzyme inhibitors

(2010) Douglas S Johnson et al.   Future Medicinal Chemistry

New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays

(2010) Jonathan B. Baell et al.   JOURNAL OF MEDICINAL CHEMISTRY

Quantitative reactivity profiling predicts functional cysteines in proteomes

(2010) Eranthie Weerapana et al.   NATURE

The Bruton tyrosine kinase inhibitor PCI-32765 blocks B-cell activation and is efficacious in models of autoimmune disease and B-cell malignancy

(2010) L. A. Honigberg et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

IC50-based approaches as an alternative method for assessment of time-dependent inhibition of CYP3A4

(2010) Howard J. Burt et al.   XENOBIOTICA

Benzothiophene piperazine and piperidine urea inhibitors of fatty acid amide hydrolase (FAAH)

(2009) Douglas S. Johnson et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Kinetic Glutathione Chemoassay To Quantify Thiol Reactivity of Organic ElectrophilesApplication to α,β-Unsaturated Ketones, Acrylates, and Propiolates

(2009) Alexander Böhme et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Discovery and Characterization of a Highly Selective FAAH Inhibitor that Reduces Inflammatory Pain

(2009) Kay Ahn et al.   CHEMISTRY & BIOLOGY

Inhibition of CYP3A by Erythromycin: In Vitro-In Vivo Correlation in Rats

(2009) X. Zhang et al.   DRUG METABOLISM AND DISPOSITION

Physiologically Based Pharmacokinetic Model of Mechanism-Based Inhibition of CYP3A by Clarithromycin

(2009) S. K. Quinney et al.   DRUG METABOLISM AND DISPOSITION

Semiphysiologically Based Pharmacokinetic Models for the Inhibition of Midazolam Clearance by Diltiazem and Its Major Metabolite

(2009) X. Zhang et al.   DRUG METABOLISM AND DISPOSITION

A Zone Classification System for Risk Assessment of Idiosyncratic Drug Toxicity Using Daily Dose and Covalent Binding

(2009) S. Nakayama et al.   DRUG METABOLISM AND DISPOSITION

Covalent Modifiers: An Orthogonal Approach to Drug Design

(2009) Michele H. Potashman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Quantitative Analyses of Aggregation, Autofluorescence, and Reactivity Artifacts in a Screen for Inhibitors of a Thiol Protease

(2009) Ajit Jadhav et al.   JOURNAL OF MEDICINAL CHEMISTRY

A Suite of Activity-Based Probes for Human Cytochrome P450 Enzymes

(2009) Aaron T. Wright et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Validation of cytochrome P450 time-dependent inhibition assays: a two-time point IC50shift approach facilitateskinactassay design

(2009) E. S. Perloff et al.   XENOBIOTICA

A Novel Class of Small Molecule Inhibitors of Hsp90

(2008) Fang Yi et al.   ACS Chemical Biology

Timing and Dynamics of Single Cell Gene Expression in the Arabinose Utilization System

(2008) Judith A. Megerle et al.   BIOPHYSICAL JOURNAL

Covalent Modification at Cys151 Dissociates the Electrophile Sensor Keap1 from the Ubiquitin Ligase CUL3

(2008) Girish Rachakonda et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Immune-Mediated Adverse Drug Reactions

(2008) Jack Uetrecht   CHEMICAL RESEARCH IN TOXICOLOGY

Covalent Inhibitors of Human Monoacylglycerol Lipase: Ligand-Assisted Characterization of the Catalytic Site by Mass Spectrometry and Mutational Analysis

(2008) Nikolai Zvonok et al.   CHEMISTRY & BIOLOGY

Prediction of the Effect of Erythromycin, Diltiazem, and Their Metabolites, Alone and in Combination, on CYP3A4 Inhibition

(2008) X. Zhang et al.   DRUG METABOLISM AND DISPOSITION

Relationship between daily dose of oral medications and idiosyncratic drug-induced liver injury: Search for signals

(2008) Craig Lammert et al.   HEPATOLOGY

Turnover of the Human Proteome: Determination of Protein Intracellular Stability by Dynamic SILAC

(2008) Mary K. Doherty et al.   JOURNAL OF PROTEOME RESEARCH