Development of Noncovalent Small-Molecule Keap1-Nrf2 Inhibitors by Fragment-Based Drug Discovery

Recapitulating the Binding Affinity of Nrf2 for KEAP1 in a Cyclic Heptapeptide, Guided by NMR, X-ray Crystallography, and Machine Learning

(2021) Paula C. Ortet et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Deconstructing Noncovalent Kelch-like ECH-Associated Protein 1 (Keap1) Inhibitors into Fragments to Reconstruct New Potent Compounds

(2021) Jakob S. Pallesen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Small-Molecule Inhibitors of Reactive Oxygen Species Production

(2021) Elisa Sassetti et al.   JOURNAL OF MEDICINAL CHEMISTRY

Molecular basis for the disruption of Keap1–Nrf2 interaction via Hinge & Latch mechanism

(2021) Yuta Horie et al.   Communications Biology

Harnessing the E3 Ligase KEAP1 for Targeted Protein Degradation

(2021) Jieli Wei et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Fragment-to-Lead Medicinal Chemistry Publications in 2020

(2021) Iwan J. P. de Esch et al.   JOURNAL OF MEDICINAL CHEMISTRY

Fragment-Guided Discovery of Pyrazole Carboxylic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2 Related Factor 2 (KEAP1:NRF2) Protein−Protein Interaction

(2021) David Norton et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of disubstituted xylylene derivatives as small molecule direct inhibitors of Keap1-Nrf2 protein-protein interaction

(2020) Dhulfiqar Ali Abed et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Recent progress in the development of small molecule Nrf2 activators: a patent review (2017-present)

(2020) Haishan Zhou et al.   EXPERT OPINION ON THERAPEUTIC PATENTS

Developing Inhibitors of the p47phox–p22phox Protein–Protein Interaction by Fragment-Based Drug Discovery

(2020) Sara Marie Øie Solbak et al.   JOURNAL OF MEDICINAL CHEMISTRY

Facts, Patterns and Principles in Drug Discovery: appraising the Rule of 5 with measured physicochemical data.

(2020) Christopher P. Tinworth et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Molecular Mechanisms Regulating the KEAP1-NRF2 Pathway

(2020) Liam Baird et al.   MOLECULAR AND CELLULAR BIOLOGY

Applied Biophysical Methods in Fragment-Based Drug Discovery

(2020) Joe Coyle et al.   SLAS Discovery

A hydrogen peroxide responsive prodrug of Keap1-Nrf2 inhibitor for improving oral absorption and selective activation in inflammatory conditions

(2020) Mengchen Lu et al.   Redox Biology

Design, Synthesis, and Structure–Activity Relationships of Indoline-Based Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-Like 2 (Keap1-Nrf2) Protein–Protein Interaction Inhibitors

(2020) Hai-Shan Zhou et al.   JOURNAL OF MEDICINAL CHEMISTRY

On the Clinical Pharmacology of Reactive Oxygen Species

(2020) Ana I. Casas et al.   PHARMACOLOGICAL REVIEWS

SARS-CoV2-mediated suppression of NRF2-signaling reveals potent antiviral and anti-inflammatory activity of 4-octyl-itaconate and dimethyl fumarate

(2020) David Olagnier et al.   Nature Communications

Discovery of 2-oxy-2-phenylacetic acid substituted naphthalene sulfonamide derivatives as potent KEAP1-NRF2 protein-protein interaction inhibitors for inflammatory conditions

(2020) Meng-Chen Lu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Mining Natural Products for Macrocycles to Drug Difficult Targets

(2020) Fabio Begnini et al.   JOURNAL OF MEDICINAL CHEMISTRY

Therapeutic targeting of the NRF2 and KEAP1 partnership in chronic diseases

(2019) Antonio Cuadrado et al.   NATURE REVIEWS DRUG DISCOVERY

Structure–Activity and Structure–Conformation Relationships of Aryl Propionic Acid Inhibitors of the Kelch-like ECH-Associated Protein 1/Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1/NRF2) Protein–Protein Interaction

(2019) Tom D. Heightman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Ranking Hits From Saturation Transfer Difference Nuclear Magnetic Resonance–Based Fragment Screening

(2019) Jonas Aretz et al.   Frontiers in Chemistry

A Comparative Assessment Study of Known Small-Molecule Keap1−Nrf2 Protein–Protein Interaction Inhibitors: Chemical Synthesis, Binding Properties, and Cellular Activity

(2019) Kim T. Tran et al.   JOURNAL OF MEDICINAL CHEMISTRY

Isoquinoline Kelch-like ECH-Associated Protein 1-Nuclear Factor (Erythroid-Derived 2)-like 2 (KEAP1-NRF2) Inhibitors with High Metabolic Stability

(2019) Phillip R. Lazzara et al.   JOURNAL OF MEDICINAL CHEMISTRY

Concepts and Core Principles of Fragment-Based Drug Design

(2019) Philine Kirsch et al.   MOLECULES

Interaction Energetics and Druggability of the Protein–Protein Interaction between Kelch-like ECH-Associated Protein 1 (KEAP1) and Nuclear Factor Erythroid 2 Like 2 (Nrf2)

(2019) Mengqi Zhong et al.   BIOCHEMISTRY

Design, synthesis and identification of novel, orally bioavailable non-covalent Nrf2 activators

(2019) Bin Ma et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Site-Selective γ-C(sp3 )−H and γ-C(sp2 )−H Arylation of Free Amino Esters Promoted by a Catalytic Transient Directing Group

(2018) Hua Lin et al.   CHEMISTRY-A EUROPEAN JOURNAL

Mapping the Efficiency and Physicochemical Trajectories of Successful Optimizations

(2018) Robert J. Young et al.   JOURNAL OF MEDICINAL CHEMISTRY

Lipophilic Efficiency as an Important Metric in Drug Design

(2018) Ted W. Johnson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Non-covalent Small-Molecule Kelch-like ECH-Associated Protein 1–Nuclear Factor Erythroid 2-Related Factor 2 (Keap1–Nrf2) Inhibitors and Their Potential for Targeting Central Nervous System Diseases

(2018) Jakob S. Pallesen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Cytochrome P450 4F11 Activated Inhibitors of Stearoyl Coenzyme A Desaturase

(2018) Sarah E. Winterton et al.   JOURNAL OF MEDICINAL CHEMISTRY

DIALS: implementation and evaluation of a new integration package

(2018) Graeme Winter et al.   Acta Crystallographica Section D-Structural Biology

Replacement of a Naphthalene Scaffold in Kelch-like ECH-Associated Protein 1 (KEAP1)/Nuclear Factor (Erythroid-derived 2)-like 2 (NRF2) Inhibitors

(2018) Benjamin G. Richardson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Two Decades under the Influence of the Rule of Five and the Changing Properties of Approved Oral Drugs

(2018) Michael D. Shultz   JOURNAL OF MEDICINAL CHEMISTRY

Itaconate is an anti-inflammatory metabolite that activates Nrf2 via alkylation of KEAP1

(2018) Evanna L. Mills et al.   NATURE

Enantioselective Conjugate Additions of 2-Alkoxycarbonyl-3(2H)-furanones

(2018) Petra Vojáčková et al.   ORGANIC LETTERS

Exploring Tandem Ruthenium-Catalyzed Hydrogen Transfer and SNAr Chemistry

(2017) Kurt Polidano et al.   ORGANIC LETTERS

AceDRG: a stereochemical description generator for ligands

(2017) Fei Long et al.   Acta Crystallographica Section D-Structural Biology

P13, the EMBL macromolecular crystallography beamline at the low-emittance PETRA III ring for high- and low-energy phasing with variable beam focusing

(2017) Michele Cianci et al.   JOURNAL OF SYNCHROTRON RADIATION

Transcriptional Regulation by Nrf2

(2017) Claudia Tonelli et al.   ANTIOXIDANTS & REDOX SIGNALING

Design, synthesis, and evaluation of 2-piperidone derivatives for the inhibition of β-amyloid aggregation and inflammation mediated neurotoxicity

(2016) Lei Li et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Efficient Synthesis ofN-Substituted 2,4-Azepandione Ring System as an Active Intermediate for Heterocyclic Syntheses

(2016) Mohamed A. Waly et al.   JOURNAL OF HETEROCYCLIC CHEMISTRY

Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein–Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery

(2016) Thomas G. Davies et al.   JOURNAL OF MEDICINAL CHEMISTRY

The Keap1-Nrf2-ARE Pathway As a Potential Preventive and Therapeutic Target: An Update

(2016) Meng-Chen Lu et al.   MEDICINAL RESEARCH REVIEWS

Twenty years on: the impact of fragments on drug discovery

(2016) Daniel A. Erlanson et al.   NATURE REVIEWS DRUG DISCOVERY

Chemical proteomic map of dimethyl fumarate–sensitive cysteines in primary human T cells

(2016) Megan M. Blewett et al.   Science Signaling

Chemical proteomic map of dimethyl fumarate–sensitive cysteines in primary human T cells

(2016) Megan M. Blewett et al.   Science Signaling

Dimethyl fumarate in the management of multiple sclerosis: appropriate patient selection and special considerations

(2016) Luca Prosperini et al.   Therapeutics and Clinical Risk Management

One Question, Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists

(2015) Johannes Schiebel et al.   ChemMedChem

Probing the structural requirements of non-electrophilic naphthalene-based Nrf2 activators

(2015) Atul D. Jain et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Characterization of RA839, a Noncovalent Small Molecule Binder to Keap1 and Selective Activator of Nrf2 Signaling

(2015) Angelika F. Winkel et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Cell-Permeable Peptide Targeting the Nrf2-Keap1 Interaction: A Potential Novel Therapy for Global Cerebral Ischemia

(2015) J. Tu et al.   JOURNAL OF NEUROSCIENCE

Dimethyl Fumarate Protects Brain From Damage Produced by Intracerebral Hemorrhage by Mechanism Involving Nrf2

(2015) Xiurong Zhao et al.   STROKE

Highly Enantioselective Michael Addition of Nitroalkanes to Enones and Its Application in Syntheses of (R)-Baclofen and (R)-Phenibut

(2015) Feng Sha et al.   SYNTHESIS-STUTTGART

Binding Mode and Structure-Activity Relationships around Direct Inhibitors of the Nrf2-Keap1 Complex

(2014) Eric Jnoff et al.   ChemMedChem

Discovery of Potent Keap1–Nrf2 Protein–Protein Interaction Inhibitor Based on Molecular Binding Determinants Analysis

(2014) Zheng-Yu Jiang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Stereoselective construction of all-carbon quaternary center by means of chiral phosphoric acid: highly enantioselective Friedel–Crafts reaction of indoles with β,β-disubstituted nitroalkenes

(2014) Keiji Mori et al.   Chemical Science

Small molecules inhibit the interaction of Nrf2 and the Keap1 Kelch domain through a non-covalent mechanism

(2013) Douglas Marcotte et al.   BIOORGANIC & MEDICINAL CHEMISTRY

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

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

Discovery of a small-molecule inhibitor and cellular probe of Keap1–Nrf2 protein–protein interaction

(2013) Longqin Hu et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

The macromolecular crystallography beamline I911-3 at the MAX IV laboratory

(2013) Thomas Ursby et al.   JOURNAL OF SYNCHROTRON RADIATION

Towards automated crystallographic structure refinement withphenix.refine

(2012) Pavel V. Afonine et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

Efficient and practical transition metal-free catalytic hydration of organonitriles to amides

(2012) Tao Tu et al.   GREEN CHEMISTRY

ID29: a high-intensity highly automated ESRF beamline for macromolecular crystallography experiments exploiting anomalous scattering

(2012) Daniele de Sanctis et al.   JOURNAL OF SYNCHROTRON RADIATION

Small Molecule Modulators of Keap1-Nrf2-ARE Pathway as Potential Preventive and Therapeutic Agents

(2012) Sadagopan Magesh et al.   MEDICINAL RESEARCH REVIEWS

Data processing and analysis with theautoPROCtoolbox

(2011) Clemens Vonrhein et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

Modeling Taylor dispersion injections: Determination of kinetic/affinity interaction constants and diffusion coefficients in label-free biosensing

(2011) John G. Quinn   ANALYTICAL BIOCHEMISTRY

Evaluation of Taylor dispersion injections: Determining kinetic/affinity interaction constants and diffusion coefficients in label-free biosensing

(2011) John G. Quinn   ANALYTICAL BIOCHEMISTRY

A novel strategy to activate cytoprotective genes in the injured brain

(2011) Jing Zhao et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ISPyB: an information management system for synchrotron macromolecular crystallography

(2011) S. Delageniere et al.   BIOINFORMATICS

Fumaric acid esters exert neuroprotective effects in neuroinflammation via activation of the Nrf2 antioxidant pathway

(2011) Ralf A. Linker et al.   BRAIN

Synthesis of Unsymmetrical 3,4-Diaryl-3-pyrrolin-2-ones Utilizing Pyrrole Weinreb Amides

(2011) Jessica G. Greger et al.   JOURNAL OF ORGANIC CHEMISTRY

Asymmetric sp3 C–H functionalization via a chiral Brønsted acid-catalyzed redox reaction for the synthesis of cyclic aminals

(2011) Yu-Ping He et al.   TETRAHEDRON LETTERS

Optimization of data collection taking radiation damage into account

(2010) Gleb P. Bourenkov et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

XDS

(2010) Wolfgang Kabsch   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

Features and development ofCoot

(2010) P. Emsley et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

The Nrf2-ARE Pathway

(2010) Jeffrey A. Johnson et al.   Annals of the New York Academy of Sciences

Observations on screening-based research and some concerning trends in the literature

(2010) Jonathan B Baell   Future Medicinal Chemistry

MxCuBE: a synchrotron beamline control environment customized for macromolecular crystallography experiments

(2010) José Gabadinho et al.   JOURNAL OF SYNCHROTRON RADIATION

Defining optimum lipophilicity and molecular weight ranges for drug candidates—Molecular weight dependent lower logD limits based on permeability

(2009) Michael J. Waring   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Solvent-Promoted and -Controlled Aza-Michael Reaction with Aromatic Amines

(2009) Kavita De et al.   JOURNAL OF ORGANIC CHEMISTRY

Convenient and versatile synthesis of formyl-substituted benzoxaboroles

(2009) Long Ye et al.   TETRAHEDRON

An aerobic ligandless palladium acetate catalysed Suzuki–Miyaura cross-coupling reaction in an aqueous solvent

(2009) Chen Li et al.   JOURNAL OF CHEMICAL RESEARCH

Surface Plasmon Resonance Based Assay for the Detection and Characterization of Promiscuous Inhibitors

(2008) Anthony M. Giannetti et al.   JOURNAL OF MEDICINAL CHEMISTRY

A facile chemoenzymatic approach to chiral non-racemic β-alkyl-γ-amino acids and 2-alkylsuccinic acids. A concise synthesis of (S)-(+)-Pregabalin

(2008) Fulvia Felluga et al.   TETRAHEDRON-ASYMMETRY