Targeted Covalent Inhibitors for Drug Design

Spiroepoxytriazoles Are Fumagillin-like Irreversible Inhibitors of MetAP2 with Potent Cellular Activity

(2016) Michael Morgen et al.   ACS Chemical Biology

Scientists in the dark after French clinical trial proves fatal

(2016) Declan Butler et al.   NATURE

The Design of Covalent Allosteric Drugs

(2015) Ruth Nussinov et al.   Annual Review of Pharmacology and Toxicology

Structure-based design and synthesis of covalent-reversible inhibitors to overcome drug resistance in EGFR

(2015) Debjit Basu et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Targeted inhibition of the Shroom3–Rho kinase protein–protein interaction circumvents Nogo66 to promote axon outgrowth

(2015) Heather M Dickson et al.   BMC NEUROSCIENCE

Label-Free Bottom-Up Proteomic Workflow for Simultaneously Assessing the Target Specificity of Covalent Drug Candidates and Their Off-Target Reactivity to Selected Proteins

(2015) Yanou Yang et al.   CHEMICAL RESEARCH IN TOXICOLOGY

A Mass Spectrometry Platform for a Streamlined Investigation of Proteasome Integrity, Posttranslational Modifications, and Inhibitor Binding

(2015) Malte Gersch et al.   CHEMISTRY & BIOLOGY

EGFR Mutations and Resistance to Irreversible Pyrimidine-Based EGFR Inhibitors

(2015) D. Ercan et al.   CLINICAL CANCER RESEARCH

An Overview of Recent Dipeptidyl Peptidase-IV Inhibitors: Linking their Structure and Physico-Chemical Properties with SAR, Pharmacokinetics and Toxicity

(2015) Andrija Smelcerovic et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Systematic Study of the Glutathione (GSH) Reactivity of N-Arylacrylamides: 1. Effects of Aryl Substitution

(2015) Victor J. Cee et al.   JOURNAL OF MEDICINAL CHEMISTRY

Identification of a novel class of covalent modifiers of hemoglobin as potential antisickling agents

(2015) A. M. Omar et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

A tag-free collisionally induced fragmentation approach to detect drug-adducted proteins by mass spectrometry

(2015) T. Eric Ballard et al.   RAPID COMMUNICATIONS IN MASS SPECTROMETRY

Identification of covalent active site inhibitors of dengue virus protease

(2015) Xiaoying Koh-Stenta et al.   Drug Design Development and Therapy

Selective Inhibition of Mutant Ras Protein through Covalent Binding

(2014) Joachim Rudolph et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Activity-Based Profiling of Proteases

(2014) Laura E. Sanman et al.   Annual Review of Biochemistry

Reversible Covalent Inhibition of eEF-2K by Carbonitriles

(2014) Ashwini K. Devkota et al.   CHEMBIOCHEM

The contributions of Sidney D. Nelson to drug metabolism research

(2014) Thomas A. Baillie   DRUG METABOLISM REVIEWS

Bruton's TK inhibitors: structural insights and evolution of clinical candidates

(2014) Li Xing et al.   Future Medicinal Chemistry

Proteasome inhibitors - molecular basis and current perspectives in multiple myeloma

(2014) Lenka Kubiczkova et al.   JOURNAL OF CELLULAR AND MOLECULAR MEDICINE

Design, Synthesis, and Characterization of α-Ketoheterocycles That Additionally Target the Cytosolic Port Cys269 of Fatty Acid Amide Hydrolase

(2014) Katerina Otrubova et al.   JOURNAL OF MEDICINAL CHEMISTRY

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 Chemical Tuned Strategy to Develop Novel Irreversible EGFR-TK Inhibitors with Improved Safety and Pharmacokinetic Profiles

(2014) Guangxin Xia et al.   JOURNAL OF MEDICINAL CHEMISTRY

Electrophilic Warhead-Based Design of Compounds Preventing NLRP3 Inflammasome-Dependent Pyroptosis

(2014) Mattia Cocco 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

Discovery of Covalent Inhibitors of Glyceraldehyde-3-phosphate Dehydrogenase, A Target for the Treatment of Malaria

(2014) Stefano Bruno et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design of Reversible, Cysteine-Targeted Michael Acceptors Guided by Kinetic and Computational Analysis

(2014) Shyam Krishnan et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

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

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

Predicting the Reactivity of Nitrile-Carrying Compounds with Cysteine: A Combined Computational and Experimental Study

(2014) Anna Berteotti et al.   ACS Medicinal Chemistry Letters

Discovery of a Selective Irreversible BMX Inhibitor for Prostate Cancer

(2013) Feiyang Liu et al.   ACS Chemical Biology

Discovery of an irreversible HCV NS5B polymerase inhibitor

(2013) Qingbei Zeng et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Drug discovery considerations in the development of covalent inhibitors

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

Benchmarking in Vitro Covalent Binding Burden As a Tool To Assess Potential Toxicity Caused by Nonspecific Covalent Binding of Covalent Drugs

(2013) Upendra P. Dahal et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Developing Irreversible Inhibitors of the Protein Kinase Cysteinome

(2013) Qingsong Liu et al.   CHEMISTRY & BIOLOGY

Discovery of a Potent and Isoform-Selective Targeted Covalent Inhibitor of the Lipid Kinase PI3Kα

(2013) Mariana Nacht et al.   JOURNAL OF MEDICINAL CHEMISTRY

Keap Calm, and Carry on Covalently

(2013) Anthony J. Wilson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure- and Reactivity-Based Development of Covalent Inhibitors of the Activating and Gatekeeper Mutant Forms of the Epidermal Growth Factor Receptor (EGFR)

(2013) Richard A. Ward et al.   JOURNAL OF MEDICINAL CHEMISTRY

Docking-Based Virtual Screening of Covalently Binding Ligands: An Orthogonal Lead Discovery Approach

(2013) Jörg Schröder et al.   JOURNAL OF MEDICINAL CHEMISTRY

Electrophilic Fragment-Based Design of Reversible Covalent Kinase Inhibitors

(2013) Rand M. Miller et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Rational Design of Fatty Acid Amide Hydrolase Inhibitors That Act by Covalently Bonding to Two Active Site Residues

(2013) Katerina Otrubova et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Irreversible kinase inhibitors gain traction

(2013) Katharine Sanderson   NATURE REVIEWS DRUG DISCOVERY

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

Irreversible Inhibitors of c-Src Kinase That Target a Nonconserved Cysteine

(2012) Frank E. Kwarcinski et al.   ACS Chemical Biology

Mass Spectrometry-Based Proteomics in Preclinical Drug Discovery

(2012) Markus Schirle et al.   CHEMISTRY & BIOLOGY

How Chemoproteomics Can Enable Drug Discovery and Development

(2012) Raymond E. Moellering et al.   CHEMISTRY & BIOLOGY

Discovery of Potent and Selective Covalent Inhibitors of JNK

(2012) Tinghu Zhang et al.   CHEMISTRY & BIOLOGY

Activity-based protein profiling: an enabling technology in chemical biology research

(2012) Nan Li et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Drug discovery for a new generation of covalent drugs

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

High lipophilicity and high daily dose of oral medications are associated with significant risk for drug-induced liver injury

(2012) Minjun Chen et al.   HEPATOLOGY

Irreversible Protein Kinase Inhibitors: Balancing the Benefits and Risks

(2012) Tjeerd Barf 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

Iminoboronates: A New Strategy for Reversible Protein Modification

(2012) Pedro M. S. D. Cal et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Selective Targeting of Distinct Active Site Nucleophiles by Irreversible Src-Family Kinase Inhibitors

(2012) Nathan N. Gushwa et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles

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

The pharmacological landscape and therapeutic potential of serine hydrolases

(2012) Daniel A. Bachovchin et al.   NATURE REVIEWS DRUG DISCOVERY

Reactive Intermediates

(2012) Terrence J. Monks et al.   TOXICOLOGIC PATHOLOGY

Afatinib pharmacokinetics and metabolism after oral administration to healthy male volunteers

(2011) Peter Stopfer et al.   CANCER CHEMOTHERAPY AND PHARMACOLOGY

Structural Alert/Reactive Metabolite Concept as Applied in Medicinal Chemistry to Mitigate the Risk of Idiosyncratic Drug Toxicity: A Perspective Based on the Critical Examination of Trends in the Top 200 Drugs Marketed in the United States

(2011) Antonia F. Stepan et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Irreversible Protein Kinase Inhibitors

(2011) L. Garuti et al.   CURRENT MEDICINAL CHEMISTRY

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

Cysteine Mapping in Conformationally Distinct Kinase Nucleotide Binding Sites: Application to the Design of Selective Covalent Inhibitors

(2011) Emeline Leproult et al.   JOURNAL OF MEDICINAL CHEMISTRY

Irreversible Nek2 Kinase Inhibitors with Cellular Activity

(2011) Jeffrey C. Henise et al.   JOURNAL OF MEDICINAL CHEMISTRY

Epidermal Growth Factor Receptor Irreversible Inhibitors: Chemical Exploration of the Cysteine-Trap Portion

(2011) C. Carmi et al.   MINI-REVIEWS IN MEDICINAL CHEMISTRY

The resurgence of covalent drugs

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

Pharmacokinetics of oral neratinib during co-administration of ketoconazole in healthy subjects

(2010) Richat Abbas et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

A Structure-Guided Approach to Creating Covalent FGFR Inhibitors

(2010) Wenjun Zhou et al.   CHEMISTRY & BIOLOGY

Targeted covalent drugs of the kinase family

(2010) Juswinder Singh et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Acylating drugs: redesigning natural covalent inhibitors

(2010) Arthur F Kluge et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Recent Advances in the Design of Cathepsin S Inhibitors

(2010) John J. M. Wiener et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

Characterization of HKI-272 Covalent Binding to Human Serum Albumin

(2010) J. Wang et al.   DRUG METABOLISM AND DISPOSITION

Strategies for discovering and derisking covalent, irreversible enzyme inhibitors

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

Selective irreversible inhibition of a protease by targeting a noncatalytic cysteine

(2010) Margit Hagel et al.   Nature Chemical Biology

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

A simple in vitro assay for assessing the reactivity of nitrile containing compounds

(2009) Philip A. MacFaul 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

Metabolic Oxidative Cleavage of Thioesters: Evidence for the Formation of Sulfenic Acid Intermediates in the Bioactivation of the Antithrombotic Prodrugs Ticlopidine and Clopidogrel

(2009) Patrick M. Dansette et al.   CHEMICAL RESEARCH IN TOXICOLOGY

Covalent Modifiers: An Orthogonal Approach to Drug Design

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

Activity-Based Proteome Profiling of Potential Cellular Targets of Orlistat − An FDA-Approved Drug with Anti-Tumor Activities

(2009) Peng-Yu Yang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Physiochemical drug properties associated with in vivo toxicological outcomes

(2008) Jason D. Hughes et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Reversibility of Covalent Electrophile−Protein Adducts and Chemical Toxicity

(2008) De Lin et al.   CHEMICAL RESEARCH IN TOXICOLOGY

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

(2008) Craig Lammert et al.   HEPATOLOGY

Beyond Picomolar Affinities: Quantitative Aspects of Noncovalent and Covalent Binding of Drugs to Proteins

(2008) Adam J. T. Smith et al.   JOURNAL OF MEDICINAL CHEMISTRY

The T790M "gatekeeper" mutation in EGFR mediates resistance to low concentrations of an irreversible EGFR inhibitor

(2008) N. Godin-Heymann et al.   MOLECULAR CANCER THERAPEUTICS

The T790M mutation in EGFR kinase causes drug resistance by increasing the affinity for ATP

(2008) C.-H. Yun et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA