Kinase-targeting small-molecule inhibitors and emerging bifunctional molecules

Degraders: The Ultimate Weapon Against Amplified Driver Kinases in Cancer

(2022) Pedro Torres-Ayuso et al.   MOLECULAR PHARMACOLOGY

Deubiquitinase-targeting chimeras for targeted protein stabilization

(2022) Nathaniel J. Henning et al.   Nature Chemical Biology

Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease

(2021) Kamakoti P. Bhat et al.   NATURE REVIEWS DRUG DISCOVERY

Recent advances in development of hetero-bivalent kinase inhibitors

(2021) Seungbeom Lee et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Phase 3 Trials of Tirbanibulin Ointment for Actinic Keratosis

(2021) Andrew Blauvelt et al.   NEW ENGLAND JOURNAL OF MEDICINE

ROCK2 Inhibition With Belumosudil (KD025) for the Treatment of Chronic Graft-Versus-Host Disease

(2021) Madan Jagasia et al.   JOURNAL OF CLINICAL ONCOLOGY

Kinase drug discovery 20 years after imatinib: progress and future directions

(2021) Philip Cohen et al.   NATURE REVIEWS DRUG DISCOVERY

Discovery and Characterisation of Highly Cooperative FAK‐Degrading PROTACs

(2021) Robert P. Law et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Trends in kinase drug discovery: targets, indications and inhibitor design

(2021) Misty M. Attwood et al.   NATURE REVIEWS DRUG DISCOVERY

PI3K inhibitors are finally coming of age

(2021) Bart Vanhaesebroeck et al.   NATURE REVIEWS DRUG DISCOVERY

Allosteric MEK inhibitors act on BRAF/MEK complexes to block MEK activation

(2021) Gonzalo L. Gonzalez-Del Pino et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Modulation of Phosphoprotein Activity by Phosphorylation Targeting Chimeras (PhosTACs)

(2021) Po-Han Chen et al.   ACS Chemical Biology

Small Molecule Kinase Inhibitor Drugs (1995–2021): Medical Indication, Pharmacology, and Synthesis

(2021) Cecilia C. Ayala-Aguilera et al.   JOURNAL OF MEDICINAL CHEMISTRY

Site-Specific Labeling of Endogenous Proteins Using CoLDR Chemistry

(2021) Rambabu N. Reddi et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Targeted Protein Acetylation in Cells Using Heterobifunctional Molecules

(2021) Wesley W. Wang et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Cataloguing the dead: breathing new life into pseudokinase research

(2020) Safal Shrestha et al.   FEBS Journal

Efficient Targeted Degradation via Reversible and Irreversible Covalent PROTACs

(2020) Ronen Gabizon et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Unifying principles of bifunctional, proximity-inducing small molecules

(2020) Christopher J. Gerry et al.   Nature Chemical Biology

Tepotinib in Non–Small-Cell Lung Cancer with MET Exon 14 Skipping Mutations

(2020) Paul K. Paik et al.   NEW ENGLAND JOURNAL OF MEDICINE

Assessing the information content of structural and protein–ligand interaction representations for the classification of kinase inhibitor binding modes via machine learning and active learning

(2020) Raquel Rodríguez-Pérez et al.   Journal of Cheminformatics

The Global Phosphorylation Landscape of SARS-CoV-2 Infection

(2020) Mehdi Bouhaddou et al.   CELL

Phosphorylation-Inducing Chimeric Small Molecules

(2020) Sachini U. Siriwardena et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a double-blind, randomised, placebo-controlled, phase 3 trial

(2020) Jean-Yves Blay et al.   LANCET ONCOLOGY

Efficacy and Safety of Tofacitinib, Baricitinib, and Upadacitinib for Rheumatoid Arthritis: A Systematic Review and Meta-Analysis

(2020) Faping Wang et al.   MAYO CLINIC PROCEEDINGS

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

(2020) Zaigham M. Khan et al.   NATURE

Capmatinib in MET Exon 14–Mutated or MET-Amplified Non–Small-Cell Lung Cancer

(2020) Jürgen Wolf et al.   NEW ENGLAND JOURNAL OF MEDICINE

The cryoelectron microscopy structure of the human CDK-activating kinase

(2020) Basil J. Greber et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Mapping the Degradable Kinome Provides a Resource for Expedited Degrader Development

(2020) Katherine A. Donovan et al.   CELL

Snapshots and ensembles of BTK and cIAP1 protein degrader ternary complexes

(2020) James Schiemer et al.   Nature Chemical Biology

Baricitinib plus Remdesivir for Hospitalized Adults with Covid-19

(2020) Andre C. Kalil et al.   NEW ENGLAND JOURNAL OF MEDICINE

First-Line Lorlatinib or Crizotinib in Advanced ALK-Positive Lung Cancer

(2020) Alice T. Shaw et al.   NEW ENGLAND JOURNAL OF MEDICINE

Targeting FLT3 mutations in AML: review of current knowledge and evidence

(2019) Naval Daver et al.   LEUKEMIA

A multi-targeted probe-based strategy to identify signaling vulnerabilities in cancers

(2019) Suman Rao et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Ripretinib (DCC-2618) Is a Switch Control Kinase Inhibitor of a Broad Spectrum of Oncogenic and Drug-Resistant KIT and PDGFRA Variants

(2019) Bryan D. Smith et al.   CANCER CELL

Alpelisib for PIK3CA-Mutated, Hormone Receptor–Positive Advanced Breast Cancer

(2019) Fabrice André et al.   NEW ENGLAND JOURNAL OF MEDICINE

Combining the Allosteric Inhibitor Asciminib with Ponatinib Suppresses Emergence of and Restores Efficacy against Highly Resistant BCR-ABL1 Mutants

(2019) Christopher A. Eide et al.   CANCER CELL

Targeted protein degradation: expanding the toolbox

(2019) Matthieu Schapira et al.   NATURE REVIEWS DRUG DISCOVERY

Heterobifunctional Molecules Induce Dephosphorylation of Kinases–A Proof of Concept Study

(2019) Sayumi Yamazoe et al.   JOURNAL OF MEDICINAL CHEMISTRY

Tivozanib versus sorafenib in patients with advanced renal cell carcinoma (TIVO-3): a phase 3, multicentre, randomised, controlled, open-label study

(2019) Brian I Rini et al.   LANCET ONCOLOGY

Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure

(2019) Timothy P. Hughes et al.   NEW ENGLAND JOURNAL OF MEDICINE

p27 allosterically activates cyclin-dependent kinase 4 and antagonizes palbociclib inhibition

(2019) Keelan Z. Guiley et al.   SCIENCE

Progress with covalent small-molecule kinase inhibitors

(2018) Zheng Zhao et al.   DRUG DISCOVERY TODAY

Unexplored therapeutic opportunities in the human genome

(2018) Tudor I. Oprea et al.   NATURE REVIEWS DRUG DISCOVERY

Kinase inhibitors: the road ahead

(2018) Fleur M. Ferguson et al.   NATURE REVIEWS DRUG DISCOVERY

Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1

(2018) Joseph Schoepfer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Osimertinib in patients with T790M mutation-positive, advanced non-small cell lung cancer: Long-Term follow-up from a pooled analysis of 2 phase 2 studies

(2018) Myung-Ju Ahn et al.   CANCER

Structural basis of PROTAC cooperative recognition for selective protein degradation

(2017) Morgan S Gadd et al.   Nature Chemical Biology

Discovery of the ROCK inhibitor netarsudil for the treatment of open-angle glaucoma

(2016) Jill M. Sturdivant et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Discovery and SAR of Novel 2,3-Dihydroimidazo[1,2-c]quinazoline PI3K Inhibitors: Identification of Copanlisib (BAY 80-6946)

(2016) William J. Scott et al.   ChemMedChem

Small-molecule kinase inhibitors: an analysis of FDA-approved drugs

(2016) Peng Wu et al.   DRUG DISCOVERY TODAY

Preclinical Characterization of G1T28: A Novel CDK4/6 Inhibitor for Reduction of Chemotherapy-Induced Myelosuppression

(2016) J. E. Bisi et al.   MOLECULAR CANCER THERAPEUTICS

A Novel RAF Kinase Inhibitor with DFG-Out-Binding Mode: High Efficacy in BRAF-Mutant Tumor Xenograft Models in the Absence of Normal Tissue Hyperproliferation

(2016) I. C. Waizenegger et al.   MOLECULAR CANCER THERAPEUTICS

Induced protein degradation: an emerging drug discovery paradigm

(2016) Ashton C. Lai et al.   NATURE REVIEWS DRUG DISCOVERY

A comprehensive map of molecular drug targets

(2016) Rita Santos et al.   NATURE REVIEWS DRUG DISCOVERY

Covalent-Allosteric Kinase Inhibitors

(2015) Jörn Weisner et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Modular PROTAC Design for the Degradation of Oncogenic BCR-ABL

(2015) Ashton C. Lai et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Mode of action of nintedanib in the treatment of idiopathic pulmonary fibrosis

(2015) Lutz Wollin et al.   EUROPEAN RESPIRATORY JOURNAL

Catalytic in vivo protein knockdown by small-molecule PROTACs

(2015) Daniel P Bondeson et al.   Nature Chemical Biology

Allosteric small-molecule kinase inhibitors

(2015) Peng Wu et al.   PHARMACOLOGY & THERAPEUTICS

Dynamics-Driven Allostery in Protein Kinases

(2015) Alexandr P. Kornev et al.   TRENDS IN BIOCHEMICAL SCIENCES

FDA-approved small-molecule kinase inhibitors

(2015) Peng Wu et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Bivalent inhibitors of protein kinases

(2014) Carrie M. Gower et al.   CRITICAL REVIEWS IN BIOCHEMISTRY AND MOLECULAR BIOLOGY

Discovery of a Potent and Selective EGFR Inhibitor (AZD9291) of Both Sensitizing and T790M Resistance Mutations That Spares the Wild Type Form of the Receptor

(2014) M. Raymond V. Finlay et al.   JOURNAL OF MEDICINAL CHEMISTRY

A small-molecule mimic of a peptide docking motif inhibits the protein kinase PDK1

(2014) T. Justin Rettenmaier et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structure of the Human FANCL RING-Ube2T Complex Reveals Determinants of Cognate E3-E2 Selection

(2014) Charlotte Hodson et al.   STRUCTURE

Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation

(2013) Pascal Furet et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Structure and Dynamic Regulation of Abl Kinases

(2013) Shoghag Panjarian et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery of Dabrafenib: A Selective Inhibitor of Raf Kinases with Antitumor Activity against B-Raf-Driven Tumors

(2013) Tara R. Rheault et al.   ACS Medicinal Chemistry Letters

Pharmacokinetics of fostamatinib, a spleen tyrosine kinase (SYK) inhibitor, in healthy human subjects following single and multiple oral dosing in three phase I studies

(2012) Muhammad Baluom et al.   BRITISH JOURNAL OF CLINICAL PHARMACOLOGY

Systems-pharmacology dissection of a drug synergy in imatinib-resistant CML

(2012) Georg E Winter et al.   Nature Chemical Biology

Reversible targeting of noncatalytic cysteines with chemically tuned electrophiles

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

Insights into the Aberrant Activity of Mutant EGFR Kinase Domain and Drug Recognition

(2012) Ketan S. Gajiwala et al.   STRUCTURE

Approaches to discover non-ATP site kinase inhibitors

(2012) Lori Krim Gavrin et al.   MedChemComm

The resurgence of covalent drugs

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

Targeting Bcr–Abl by combining allosteric with ATP-binding-site inhibitors

(2010) Jianming Zhang et al.   NATURE

Protein kinases: evolution of dynamic regulatory proteins

(2010) Susan S. Taylor et al.   TRENDS IN BIOCHEMICAL SCIENCES

Through the “Gatekeeper Door”: Exploiting the Active Kinase Conformation

(2009) Fabio Zuccotto et al.   JOURNAL OF MEDICINAL CHEMISTRY

A helix scaffold for the assembly of active protein kinases

(2008) A. P. Kornev et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

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