Structural features of the protein kinase domain and targeted binding by small-molecule inhibitors

Properties of FDA-approved small molecule protein kinase inhibitors: a 2021 update

(2021) Robert Roskoski   PHARMACOLOGICAL RESEARCH

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

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

Kincore: a web resource for structural classification of protein kinases and their inhibitors

(2021) Vivek Modi et al.   NUCLEIC ACIDS RESEARCH

The structure of human GCN2 reveals a parallel, back-to-back kinase dimer with a plastic DFG activation loop motif

(2020) Taiana Maia de Oliveira et al.   BIOCHEMICAL JOURNAL

Emerging roles of the αC‐β4 loop in protein kinase structure, function, evolution, and disease

(2020) Wayland Yeung et al.   IUBMB LIFE

Nek7 conformational flexibility and inhibitor binding probed through protein engineering of the R-spine

(2020) Matthew J. Byrne et al.   BIOCHEMICAL JOURNAL

A systematic molecular and pharmacologic evaluation of AKT inhibitors reveals new insight into their biological activity

(2020) Eleftherios Kostaras et al.   BRITISH JOURNAL OF CANCER

Discovery of a selective inhibitor of doublecortin like kinase 1

(2020) Fleur M. Ferguson et al.   Nature Chemical Biology

RAF kinase dimerization: implications for drug discovery and clinical outcomes

(2020) Tilman Brummer et al.   ONCOGENE

Synthesis and Structure–Activity Relationships of DCLK1 Kinase Inhibitors Based on a 5,11-Dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one Scaffold

(2020) Fleur M. Ferguson et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Roblitinib (FGF401) as a Reversible-Covalent Inhibitor of the Kinase Activity of Fibroblast Growth Factor Receptor 4

(2020) Robin A. Fairhurst et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

(2020) Zaigham M. Khan et al.   NATURE

Kinase inhibition in autoimmunity and inflammation

(2020) Ali A. Zarrin et al.   NATURE REVIEWS DRUG DISCOVERY

The role of stress kinases in metabolic disease

(2020) Ivana Nikolic et al.   Nature Reviews Endocrinology

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

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

Conformational states dynamically populated by a kinase determine its function

(2020) Tao Xie et al.   SCIENCE

Inhibitors of BRAF dimers using an allosteric site

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

Structural basis of the (in)activity of the apical DNA damage response kinases ATM, ATR and DNA-PKcs

(2020) Marijke Jansma et al.   PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY

Defining a new nomenclature for the structures of active and inactive kinases

(2019) Vivek Modi et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Single and dual targeting of mutant EGFR with an allosteric inhibitor

(2019) Ciric To et al.   Cancer Discovery

Identification and characterization of a BRAF fusion oncoprotein with retained autoinhibitory domains

(2019) Florian Weinberg et al.   ONCOGENE

Identification of Novel, Potent, and Orally Available GCN2 Inhibitors with Type I Half Binding Mode

(2019) Jun Fujimoto et al.   ACS Medicinal Chemistry Letters

Targeting Oncogenic BRAF: Past, Present, and Future

(2019) Zaman et al.   Cancers

Discovery and Optimization of Dibenzodiazepinones as Allosteric Mutant-Selective EGFR Inhibitors

(2019) Dries J. H. De Clercq et al.   ACS Medicinal Chemistry Letters

New Promise and Opportunities for Allosteric Kinase Inhibitors

(2019) Xiaoyun Lu et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

The Cysteinome of Protein Kinases as a Target in Drug Development

(2018) Apirat Chaikuad et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Kinase inhibitors: the road ahead

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

Type II kinase inhibitors targeting Cys-gatekeeper kinases display orthogonality with wild type and Ala/Gly-gatekeeper kinases

(2018) Cory A. Ocasio et al.   ACS Chemical Biology

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

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

Structure, activation and dysregulation of fibroblast growth factor receptor kinases: perspectives for clinical targeting

(2018) Brendan Farrell et al.   BIOCHEMICAL SOCIETY TRANSACTIONS

Small molecule inhibitors targeting the EGFR/ErbB family of protein-tyrosine kinases in human cancers

(2018) Robert Roskoski   PHARMACOLOGICAL RESEARCH

Quantitative conformational profiling of kinase inhibitors reveals origins of selectivity for Aurora kinase activation states

(2018) Eric W. Lake et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Structure, biochemistry, and biology of PAK kinases

(2017) Rakesh Kumar et al.   GENE

Determining Cysteines Available for Covalent Inhibition Across the Human Kinome

(2017) Zheng Zhao et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure of PINK1 in complex with its substrate ubiquitin

(2017) Alexander F. Schubert et al.   NATURE

The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1

(2017) Andrew A. Wylie et al.   NATURE

Structure of PINK1 and mechanisms of Parkinson's disease-associated mutations

(2017) Atul Kumar et al.   eLife

Activation Mechanism of Oncogenic Deletion Mutations in BRAF, EGFR, and HER2

(2016) Scott A. Foster et al.   CANCER CELL

Discovery of 3-(3-(4-(1-Aminocyclobutyl)phenyl)-5-phenyl-3H-imidazo[4,5-b]pyridin-2-yl)pyridin-2-amine (ARQ 092): An Orally Bioavailable, Selective, and Potent Allosteric AKT Inhibitor

(2016) Jean-Marc Lapierre et al.   JOURNAL OF MEDICINAL CHEMISTRY

Overcoming EGFR(T790M) and EGFR(C797S) resistance with mutant-selective allosteric inhibitors

(2016) Yong Jia et al.   NATURE

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

(2016) Robert Roskoski   PHARMACOLOGICAL RESEARCH

ERK5 kinase activity is dispensable for cellular immune response and proliferation

(2016) Emme C. K. Lin et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Discovery of a Series of 5,11-Dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-ones as Selective PI3K-δ/γ Inhibitors

(2016) Fleur M. Ferguson et al.   ACS Medicinal Chemistry Letters

Allosteric inhibition of Aurora-A kinase by a synthetic vNAR domain

(2016) Selena G. Burgess et al.   Open Biology

Allosteric modulation of AURKA kinase activity by a small-molecule inhibitor of its protein-protein interaction with TPX2

(2016) Matej Janeček et al.   Scientific Reports

Kinase hinge binding scaffolds and their hydrogen bond patterns

(2015) Li Xing et al.   BIOORGANIC & MEDICINAL CHEMISTRY

Ten things you should know about protein kinases: IUPHAR Review 14

(2015) Doriano Fabbro et al.   BRITISH JOURNAL OF PHARMACOLOGY

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

Identification and Characterization of Tyrosine Kinase Nonreceptor 2 Mutations in Leukemia through Integration of Kinase Inhibitor Screening and Genomic Analysis

(2015) J. E. Maxson et al.   CANCER RESEARCH

Small-Molecule Allosteric Modulators of the Protein Kinase PDK1 from Structure-Based Docking

(2015) T. Justin Rettenmaier et al.   JOURNAL OF MEDICINAL CHEMISTRY

The ins and outs of selective kinase inhibitor development

(2015) Susanne Müller et al.   Nature Chemical Biology

Optimization of a Dibenzodiazepine Hit to a Potent and Selective Allosteric PAK1 Inhibitor

(2015) Alexei S. Karpov et al.   ACS Medicinal Chemistry Letters

Mechanistic basis of Nek7 activation through Nek9 binding and induced dimerization

(2015) Tamanna Haq et al.   Nature Communications

First Selective Small Molecule Inhibitor of FGFR4 for the Treatment of Hepatocellular Carcinomas with an Activated FGFR4 Signaling Pathway

(2015) M. Hagel et al.   Cancer Discovery

Molecular mechanisms of human IRE1 activation through dimerization and ligand binding

(2015) Amar Joshi et al.   Oncotarget

Pan-Cancer Analysis of Mutation Hotspots in Protein Domains

(2015) Martin L. Miller et al.   Cell Systems

Growth-Inhibitory and Antiangiogenic Activity of the MEK Inhibitor PD0325901 in Malignant Melanoma with or without BRAF Mutations

(2015) Ludovica Ciuffreda et al.   NEOPLASIA

XMD8-92 inhibits pancreatic tumor xenograft growth via a DCLK1-dependent mechanism

(2014) Sripathi M. Sureban et al.   CANCER LETTERS

Kinase Regulation by Hydrophobic Spine Assembly in Cancer

(2014) Jiancheng Hu et al.   MOLECULAR AND CELLULAR BIOLOGY

Small molecule kinase inhibitor LRRK2-IN-1 demonstrates potent activity against colorectal and pancreatic cancer through inhibition of doublecortin-like kinase 1

(2014) Nathaniel Weygant et al.   Molecular Cancer

Kinase Drug Discovery – What’s Next in the Field?

(2013) Philip Cohen et al.   ACS Chemical Biology

Developing Irreversible Inhibitors of the Protein Kinase Cysteinome

(2013) Qingsong Liu et al.   CHEMISTRY & BIOLOGY

The Structural Basis for Control of Eukaryotic Protein Kinases

(2012) Jane A. Endicott et al.   Annual Review of Biochemistry

αC helix displacement as a general approach for allosteric modulation of protein kinases

(2012) Lorenzo Palmieri et al.   DRUG DISCOVERY TODAY

RASMutations in Cutaneous Squamous-Cell Carcinomas in Patients Treated with BRAF Inhibitors

(2012) Fei Su et al.   NEW ENGLAND JOURNAL OF MEDICINE

Selective Aurora Kinase Inhibitors Identified Using a Taxol-Induced Checkpoint Sensitivity Screen

(2011) Nicholas Kwiatkowski et al.   ACS Chemical Biology

Allosteric Regulation of Protein Kinase PKCζ by the N-Terminal C1 Domain and Small Compounds to the PIF-Pocket

(2011) Laura A. Lopez-Garcia et al.   CHEMISTRY & BIOLOGY

High-Throughput Kinase Profiling: A More Efficient Approach toward the Discovery of New Kinase Inhibitors

(2011) Chandrasekhar V. Miduturu et al.   CHEMISTRY & BIOLOGY

First-in-Man Clinical Trial of the Oral Pan-AKT Inhibitor MK-2206 in Patients With Advanced Solid Tumors

(2011) Timothy A. Yap et al.   JOURNAL OF CLINICAL ONCOLOGY

Irreversible Nek2 Kinase Inhibitors with Cellular Activity

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

Catalytic Control in the EGF Receptor and Its Connection to General Kinase Regulatory Mechanisms

(2011) Natalia Jura et al.   MOLECULAR CELL

Characterization of a selective inhibitor of the Parkinson's disease kinase LRRK2

(2011) Xianming Deng et al.   Nature Chemical Biology

Structural Insights into the Autoactivation Mechanism of p21-Activated Protein Kinase

(2011) Jue Wang et al.   STRUCTURE

Crystal structure of an Aurora-A mutant that mimics Aurora-B bound to MLN8054: insights into selectivity and drug design

(2010) Charlotte A. Dodson et al.   BIOCHEMICAL JOURNAL

Inhibitors of the Abl kinase directed at either the ATP- or myristate-binding site

(2010) Doriano Fabbro et al.   BIOCHIMICA ET BIOPHYSICA ACTA-PROTEINS AND PROTEOMICS

Binding or Bending: Distinction of Allosteric Abl Kinase Agonists from Antagonists by an NMR-Based Conformational Assay

(2010) Wolfgang Jahnke et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

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

(2010) Jianming Zhang et al.   NATURE

Crystal Structure of Human AKT1 with an Allosteric Inhibitor Reveals a New Mode of Kinase Inhibition

(2010) Wen-I Wu et al.   PLoS One

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

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

An Autoinhibitory Tyrosine Motif in the Cell-Cycle-Regulated Nek7 Kinase Is Released through Binding of Nek9

(2009) Mark W. Richards et al.   MOLECULAR CELL

Knowledge Based Prediction of Ligand Binding Modes and Rational Inhibitor Design for Kinase Drug Discovery

(2008) Arup K. Ghose et al.   JOURNAL OF MEDICINAL CHEMISTRY

High-throughput kinase profiling as a platform for drug discovery

(2008) David M. Goldstein et al.   NATURE REVIEWS DRUG DISCOVERY