Mechanistic enzymology in drug discovery: a fresh perspective

Covalent inhibitors design and discovery

(2017) Stephane De Cesco et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Mechanism-based inactivator of isocitrate lyases 1 and 2 fromMycobacterium tuberculosis

(2017) Truc V. Pham et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Integrating biophysics with HTS-driven drug discovery projects

(2016) Rutger H.A. Folmer   DRUG DISCOVERY TODAY

Biophysics in drug discovery: impact, challenges and opportunities

(2016) Jean-Paul Renaud et al.   NATURE REVIEWS DRUG DISCOVERY

Transition state for the NSD2-catalyzed methylation of histone H3 lysine 36

(2016) Myles B. Poulin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Transition States and Transition State Analogue Interactions with Enzymes

(2015) Vern L. Schramm   ACCOUNTS OF CHEMICAL RESEARCH

Unknown unknowns in biomedical research: does an inability to deal with ambiguity contribute to issues of irreproducibility?

(2015) Kevin Mullane et al.   BIOCHEMICAL PHARMACOLOGY

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

(2015) Renato A. Bauer   DRUG DISCOVERY TODAY

Translating slow-binding inhibition kinetics into cellular and in vivo effects

(2015) Grant K Walkup et al.   Nature Chemical Biology

Tackling reproducibility in academic preclinical drug discovery

(2015) Stephen V. Frye et al.   NATURE REVIEWS DRUG DISCOVERY

A dynamically coupled allosteric network underlies binding cooperativity in Src kinase

(2015) Zachariah H. Foda et al.   Nature Communications

Slow Inhibition and Conformation Selective Properties of Extracellular Signal-Regulated Kinase 1 and 2 Inhibitors

(2014) Johannes Rudolph et al.   BIOCHEMISTRY

HTS followed by NMR based counterscreening. Discovery and optimization of pyrimidones as reversible and competitive inhibitors of xanthine oxidase

(2014) Johan Evenäs et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Quantification of frequent-hitter behavior based on historical high-throughput screening data

(2014) J Willem M Nissink et al.   Future Medicinal Chemistry

Biochemical, Cellular, and Biophysical Characterization of a Potent Inhibitor of Mutant Isocitrate Dehydrogenase IDH1

(2014) Mindy I. Davis et al.   JOURNAL OF BIOLOGICAL 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

Lessons learned from the fate of AstraZeneca's drug pipeline: a five-dimensional framework

(2014) David Cook et al.   NATURE REVIEWS DRUG DISCOVERY

(R)-PFI-2 is a potent and selective inhibitor of SETD7 methyltransferase activity in cells

(2014) D. Barsyte-Lovejoy et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Pharmacokinetics and the drug–target residence time concept

(2013) Göran Dahl et al.   DRUG DISCOVERY TODAY

A century of enzyme kinetic analysis, 1913 to 2013

(2013) Kenneth A. Johnson   FEBS LETTERS

Comparability of Mixed IC50 Data – A Statistical Analysis

(2013) Tuomo Kalliokoski et al.   PLoS One

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

Transition States, Analogues, and Drug Development

(2012) Vern L. Schramm   ACS Chemical Biology

Biophysical and Mechanistic Insights into Novel Allosteric Inhibitor of Spleen Tyrosine Kinase

(2012) Justin Hall et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Stoichiometry of chromatin-associated protein complexes revealed by label-free quantitative mass spectrometry-based proteomics

(2012) Arne H. Smits et al.   NUCLEIC ACIDS RESEARCH

Metal Impurities Cause False Positives in High-Throughput Screening Campaigns

(2012) Johannes C. Hermann et al.   ACS Medicinal Chemistry Letters

Impact of enzyme concentration and residence time on apparent activity recovery in jump dilution analysis

(2011) Robert A. Copeland et al.   ANALYTICAL BIOCHEMISTRY

The Moderately Efficient Enzyme: Evolutionary and Physicochemical Trends Shaping Enzyme Parameters

(2011) Arren Bar-Even et al.   BIOCHEMISTRY

Fragment screening to predict druggability (ligandability) and lead discovery success

(2011) Fredrik N.B. Edfeldt et al.   DRUG DISCOVERY TODAY

KNIME Workflow to Assess PAINS Filters in SMARTS Format. Comparison of RDKit and Indigo Cheminformatics Libraries

(2011) Simon Saubern et al.   Molecular Informatics

The resurgence of covalent drugs

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

Believe it or not: how much can we rely on published data on potential drug targets?

(2011) Florian Prinz et al.   NATURE REVIEWS DRUG DISCOVERY

Kinetic Mechanism and Rate-Limiting Steps of Focal Adhesion Kinase-1

(2010) Jessica L. Schneck et al.   BIOCHEMISTRY

Non-ATP Competitive Protein Kinase Inhibitors

(2010) L. Garuti et al.   CURRENT MEDICINAL CHEMISTRY

Apparent activity in high-throughput screening: origins of compound-dependent assay interference

(2010) Natasha Thorne et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

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

Affinity-based screening techniques: their impact and benefit to increase the number of high quality leads

(2010) Christian Bergsdorf et al.   Expert Opinion on Drug Discovery

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

Affinity-based, biophysical methods to detect and analyze ligand binding to recombinant proteins: Matching high information content with high throughput

(2010) Geoff A. Holdgate et al.   JOURNAL OF STRUCTURAL BIOLOGY

Characterizing the Effects of the Juxtamembrane Domain on Vascular Endothelial Growth Factor Receptor-2 Enzymatic Activity, Autophosphorylation, and Inhibition by Axitinib

(2009) James Solowiej et al.   BIOCHEMISTRY

Enzymatic Characterization of c-Met Receptor Tyrosine Kinase Oncogenic Mutants and Kinetic Studies with Aminopyridine and Triazolopyrazine Inhibitors

(2009) Sergei L. Timofeevski et al.   BIOCHEMISTRY

Potent Inhibitors of HIV-1 Integrase Display a Two-Step, Slow-Binding Inhibition Mechanism Which Is Absent in a Drug-Resistant T66I/M154I Mutant

(2009) Edward P. Garvey et al.   BIOCHEMISTRY

IMP Dehydrogenase: Structure, Mechanism, and Inhibition

(2009) Lizbeth Hedstrom   CHEMICAL REVIEWS

Mechanism of PDK1-catalyzed Thr-229 Phosphorylation of the S6K1 Protein Kinase

(2009) Malik M. Keshwani et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

The Target of the NSD Family of Histone Lysine Methyltransferases Depends on the Nature of the Substrate

(2009) Yan Li et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Cancer-associated IDH1 mutations produce 2-hydroxyglutarate

(2009) Lenny Dang et al.   NATURE

Chemical Mechanism of a Cysteine Protease, Cathepsin C, As Revealed by Integration of both Steady-State and Pre-Steady-State Solvent Kinetic Isotope Effects

(2008) Jessica L. Schneck et al.   BIOCHEMISTRY