Analysis of the ERK Pathway Cysteinome for Targeted Covalent Inhibition of RAF and MEK Kinases

Covalent Proximity Scanning of a Distal Cysteine to Target PI3Kα

(2022) Chiara Borsari et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Phase I Targeted Combination Trial of Sorafenib and GW5074 in Patients with Advanced Refractory Solid Tumors

(2022) Chien-Chang Kao et al.   Journal of Clinical Medicine

The Synergistic Cytotoxic Effects of GW5074 and Sorafenib by Impacting Mitochondrial Functions in Human Colorectal Cancer Cell Lines

(2022) Je-Ming Hu et al.   Frontiers in Oncology

Fragment-Based Discovery of Novel Allosteric MEK1 Binders

(2021) Paolo Di Fruscia et al.   ACS Medicinal Chemistry Letters

Exploiting allosteric properties of RAF and MEK inhibitors to target therapy-resistant tumors driven by oncogenic BRAF signaling

(2021) Christos Adamopoulos et al.   Cancer Discovery

ARAF mutations confer resistance to the RAF inhibitor belvarafenib in melanoma

(2021) Ivana Yen et al.   NATURE

Discover Novel Covalent Inhibitors Targeting FLT3 through Hybrid Virtual Screening Strategy

(2021) Shengquan Hu et al.   BIOLOGICAL & PHARMACEUTICAL BULLETIN

Structure-activity relationship study of THZ531 derivatives enables the discovery of BSJ-01-175 as a dual CDK12/13 covalent inhibitor with efficacy in Ewing sarcoma

(2021) Baishan Jiang et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Reactivities of the Front Pocket N-Terminal Cap Cysteines in Human Kinases

(2021) Ruibin Liu et al.   JOURNAL OF MEDICINAL CHEMISTRY

CovPDB: a high-resolution coverage of the covalent protein–ligand interactome

(2021) Mingjie Gao et al.   NUCLEIC ACIDS RESEARCH

A Quantitative Tissue-Specific Landscape of Protein Redox Regulation during Aging

(2020) Haopeng Xiao et al.   CELL

Targeting MAPK Signaling in Cancer: Mechanisms of Drug Resistance and Sensitivity

(2020) Shannon Lee et al.   INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

Discovery of Selective, Covalent FGFR4 Inhibitors with Anti-tumor Activity in Models of Hepato-cellular Carcinoma

(2020) Haibo Liu et al.   ACS Medicinal Chemistry Letters

Predicting Reactive Cysteines with Implicit-Solvent-Based Continuous Constant pH Molecular Dynamics in Amber

(2020) Robert C. Harris et al.   Journal of Chemical Theory and Computation

Selumetinib in Children with Inoperable Plexiform Neurofibromas

(2020) Andrea M. Gross et al.   NEW ENGLAND JOURNAL OF MEDICINE

ERK signalling: a master regulator of cell behaviour, life and fate

(2020) Hugo Lavoie et al.   NATURE REVIEWS MOLECULAR CELL BIOLOGY

Assessment of proton-coupled conformational dynamics of SARS and MERS coronavirus papain-like proteases: Implication for designing broad-spectrum antiviral inhibitors

(2020) Jack A. Henderson et al.   JOURNAL OF CHEMICAL PHYSICS

Structural basis for the action of the drug trametinib at KSR-bound MEK

(2020) Zaigham M. Khan et al.   NATURE

KLIFS: an overhaul after the first 5 years of supporting kinase research

(2020) Georgi K Kanev et al.   NUCLEIC ACIDS RESEARCH

Thiol-based michael-type addition. A systematic evaluation of its controlling factors

(2020) Arianna Gennari et al.   TETRAHEDRON

Inhibitors of BRAF dimers using an allosteric site

(2020) Xiomaris M. Cotto-Rios et al.   Nature Communications

Conformational flexibility and inhibitor binding to unphosphorylated interleukin-1 receptor–associated kinase 4 (IRAK4)

(2019) Li Wang et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Complete Regression of Advanced Pancreatic Ductal Adenocarcinomas upon Combined Inhibition of EGFR and C-RAF

(2019) María Teresa Blasco et al.   CANCER CELL

Belvarafenib, a novel pan-RAF inhibitor, in solid tumor patients harboring BRAF, KRAS, or NRAS mutations: Phase I study.

(2019) Tae Won Kim et al.   JOURNAL OF CLINICAL ONCOLOGY

Design and Discovery of N-(3-(2-(2-Hydroxyethoxy)-6-morpholinopyridin-4-yl)-4-methylphenyl)-2-(trifluoromethyl)isonicotinamide, a Selective, Efficacious, and Well-Tolerated RAF Inhibitor Targeting RAS Mutant Cancers: The Path to the Clinic

(2019) Savithri Ramurthy et al.   JOURNAL OF MEDICINAL CHEMISTRY

Assessing Lysine and Cysteine Reactivities for Designing Targeted Covalent Kinase Inhibitors

(2019) Ruibin Liu et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

GPU-Accelerated Implementation of Continuous Constant pH Molecular Dynamics in Amber: pKa Predictions with Single-pH Simulations

(2019) Robert C. Harris et al.   Journal of Chemical Information and Modeling

A Phase 1 Study of LY3009120, a Pan-RAF Inhibitor, in Patients with Advanced or Metastatic Cancer

(2019) Ryan J. Sullivan et al.   MOLECULAR CANCER THERAPEUTICS

A First-in-Human Phase I Study to Evaluate the ERK1/2 Inhibitor GDC-0994 in Patients with Advanced Solid Tumors

(2019) Andrea Varga et al.   CLINICAL CANCER RESEARCH

Development of encorafenib for BRAF-mutated advanced melanoma

(2018) Peter Koelblinger et al.   CURRENT OPINION IN ONCOLOGY

Progress with covalent small-molecule kinase inhibitors

(2018) Zheng Zhao et al.   DRUG DISCOVERY TODAY

BRAF and MEK Inhibitors: Use and Resistance in BRAF-Mutated Cancers

(2018) Jaquelyn N. Sanchez et al.   DRUGS

Generalized Born Based Continuous Constant pH Molecular Dynamics in Amber: Implementation, Benchmarking and Analysis

(2018) Yandong Huang et al.   Journal of Chemical Information and Modeling

Current Insights of BRAF Inhibitors in Cancer

(2018) Bogos Agianian et al.   JOURNAL OF MEDICINAL CHEMISTRY

SWISS-MODEL: homology modelling of protein structures and complexes

(2018) Andrew Waterhouse et al.   NUCLEIC ACIDS RESEARCH

E6201, an intravenous MEK1 inhibitor, achieves an exceptional response in BRAF V600E-mutated metastatic malignant melanoma with brain metastases

(2018) Hani M. Babiker et al.   INVESTIGATIONAL NEW DRUGS

Emerging and Re-Emerging Warheads for Targeted Covalent Inhibitors: Applications in Medicinal Chemistry and Chemical Biology

(2018) Matthias Gehringer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Expanding the Armory: Predicting and Tuning Covalent Warhead Reactivity

(2017) Richard Lonsdale et al.   Journal of Chemical Information and Modeling

Evaluation of Methods for the Calculation of the pKa of Cysteine Residues in Proteins

(2016) Ernest Awoonor-Williams et al.   Journal of Chemical Theory and Computation

Proteome-wide covalent ligand discovery in native biological systems

(2016) Keriann M. Backus et al.   NATURE

Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors

(2016) Tinghu Zhang et al.   Nature Chemical Biology

Classification of small molecule protein kinase inhibitors based upon the structures of their drug-enzyme complexes

(2016) Robert Roskoski   PHARMACOLOGICAL RESEARCH

A Perspective on the Kinetics of Covalent and Irreversible Inhibition

(2016) John M. Strelow   SLAS Discovery

Inhibition of RAF Isoforms and Active Dimers by LY3009120 Leads to Anti-tumor Activities in RAS or BRAF Mutant Cancers

(2015) Sheng-Bin Peng et al.   CANCER CELL

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

(2015) Renato A. Bauer   DRUG DISCOVERY TODAY

Quantum Mechanics/Molecular Mechanics Modeling of Covalent Addition between EGFR–Cysteine 797 and N-(4-Anilinoquinazolin-6-yl) Acrylamide

(2015) Luigi Capoferri et al.   Journal of Chemical Information and Modeling

ff14SB: Improving the Accuracy of Protein Side Chain and Backbone Parameters from ff99SB

(2015) James A. Maier et al.   Journal of Chemical Theory and Computation

Structure-Guided Design of Highly Selective and Potent Covalent Inhibitors of ERK1/2

(2015) Richard A. Ward et al.   JOURNAL OF MEDICINAL CHEMISTRY

The pKa Value and Accessibility of Cysteine Residues Are Key Determinants for Protein Substrate Discrimination by Glutaredoxin

(2014) Kristine Steen Jensen et al.   BIOCHEMISTRY

Targeting transcription regulation in cancer with a covalent CDK7 inhibitor

(2014) Nicholas Kwiatkowski et al.   NATURE

Clinical development of dabrafenib in BRAF mutant melanoma and other malignancies

(2013) Geoffrey T Gibney et al.   Expert Opinion on Drug Metabolism & Toxicology

Improved Generalized Born Solvent Model Parameters for Protein Simulations

(2013) Hai Nguyen et al.   Journal of Chemical Theory and Computation

KLIFS: A Knowledge-Based Structural Database To Navigate Kinase–Ligand Interaction Space

(2013) Oscar P. J. van Linden et al.   JOURNAL OF MEDICINAL CHEMISTRY

Understanding the pKa of Redox Cysteines: The Key Role of Hydrogen Bonding

(2012) Goedele Roos et al.   ANTIOXIDANTS & REDOX SIGNALING

Affinity-Based Probes Based on Type II Kinase Inhibitors

(2012) Pratistha Ranjitkar et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Safety, pharmacokinetic, pharmacodynamic, and efficacy data for the oral MEK inhibitor trametinib: a phase 1 dose-escalation trial

(2012) Jeffrey R Infante et al.   LANCET ONCOLOGY

H++ 3.0: automating pK prediction and the preparation of biomolecular structures for atomistic molecular modeling and simulations

(2012) R. Anandakrishnan et al.   NUCLEIC ACIDS RESEARCH

Analysis and Functional Prediction of Reactive Cysteine Residues

(2011) Stefano M. Marino et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Continuous Constant pH Molecular Dynamics in Explicit Solvent with pH-Based Replica Exchange

(2011) Jason A. Wallace et al.   Journal of Chemical Theory and Computation

Improved Treatment of Ligands and Coupling Effects in Empirical Calculation and Rationalization of pKaValues

(2011) Chresten R. Søndergaard et al.   Journal of Chemical Theory and Computation

PROPKA3: Consistent Treatment of Internal and Surface Residues in Empirical pKaPredictions

(2011) Mats H. M. Olsson et al.   Journal of Chemical Theory and Computation

RAF inhibitor resistance is mediated by dimerization of aberrantly spliced BRAF(V600E)

(2011) Poulikos I. Poulikakos et al.   NATURE

Chemical genetic strategy for targeting protein kinases based on covalent complementarity

(2011) A. L. Garske et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Kinase-Dead BRAF and Oncogenic RAS Cooperate to Drive Tumor Progression through CRAF

(2010) Sonja J. Heidorn et al.   CELL

RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF

(2010) Poulikos I. Poulikakos et al.   NATURE

RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth

(2010) Georgia Hatzivassiliou et al.   NATURE

Clinical efficacy of a RAF inhibitor needs broad target blockade in BRAF-mutant melanoma

(2010) Gideon Bollag et al.   NATURE

Quantitative reactivity profiling predicts functional cysteines in proteomes

(2010) Eranthie Weerapana et al.   NATURE

Fpocket: An open source platform for ligand pocket detection

(2009) Vincent Le Guilloux et al.   BMC BIOINFORMATICS

CHARMM: The biomolecular simulation program

(2009) B. R. Brooks et al.   JOURNAL OF COMPUTATIONAL CHEMISTRY

Therapeutic strategies for inhibiting oncogenic BRAF signaling

(2008) Ensar Halilovic et al.   CURRENT OPINION IN PHARMACOLOGY

6-Ethynylthieno[3,2-d]- and 6-ethynylthieno[2,3-d]pyrimidin-4-anilines as tunable covalent modifiers of ErbB kinases

(2008) E. R. Wood et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA