Principles of Kinase Allosteric Inhibition and Pocket Validation

Systematic comparison of competitive and allosteric kinase inhibitors reveals common structural characteristics

(2021) Huabin Hu et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Structure- and Similarity-Based Survey of Allosteric Kinase Inhibitors, Activators, and Closely Related Compounds

(2021) Oliver Laufkötter et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

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

New Horizons in Drug Discovery - Understanding and Advancing Different Types of Kinase Inhibitors: Seven Years in Kinase Inhibitor Research with Impressive Achievements and New Future Prospects

(2021) Stefan Laufer et al.   JOURNAL OF MEDICINAL CHEMISTRY

Cooperativity Between Orthosteric Inhibitors and Allosteric Inhibitor 8-Anilino-1-Naphthalene Sulfonic Acid (ANS) in Cyclin-Dependent Kinase 2

(2020) Erik B. Faber et al.   ACS Chemical Biology

Medicinal Chemistry Strategies for the Development of Kinase Inhibitors Targeting Point Mutations

(2020) Xiaoyun Lu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Selumetinib in Children with Inoperable Plexiform Neurofibromas

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

Allosteric Modulator Discovery: From Serendipity to Structure-Based Design

(2019) Shaoyong Lu et al.   JOURNAL OF MEDICINAL CHEMISTRY

Tuning the “violin” of protein kinases: The role of dynamics‐based allostery

(2019) Lalima G. Ahuja et al.   IUBMB LIFE

Kinase Atlas: Druggability Analysis of Potential Allosteric Sites in Kinases

(2019) Christine Yueh et al.   JOURNAL OF MEDICINAL CHEMISTRY

Highly Selective Inhibition of Tyrosine Kinase 2 (TYK2) for the Treatment of Autoimmune Diseases: Discovery of the Allosteric Inhibitor BMS-986165

(2019) Stephen T. Wrobleski et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

New Promise and Opportunities for Allosteric Kinase Inhibitors

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

Leveraging Structural Diversity and Allosteric Regulatory Mechanisms of Protein Kinases in the Discovery of Small Molecule Inhibitors

(2018) Gennady M. Verkhivker   CURRENT MEDICINAL CHEMISTRY

Exploration and Comparison of the Geometrical and Physicochemical Properties of an αC Allosteric Pocket in the Structural Kinome

(2018) Noé Sturm et al.   Journal of Chemical Information and Modeling

Discovery of Allosteric, Potent, Subtype Selective, and Peripherally Restricted TrkA Kinase Inhibitors

(2018) Sharan K. Bagal et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

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

The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1

(2017) Andrew A. Wylie et al.   NATURE

The target landscape of clinical kinase drugs

(2017) Susan Klaeger et al.   SCIENCE

METRIC phase III study: Efficacy of trametinib (T), a potent and selective MEK inhibitor (MEKi), in progression-free survival (PFS) and overall survival (OS), compared with chemotherapy (C) in patients (pts) with BRAFV600E/K mutant advanced or metastatic melanoma (MM).

(2017) Caroline Robert et al.   JOURNAL OF CLINICAL ONCOLOGY

Discovery and Characterization of Allosteric WNK Kinase Inhibitors

(2016) Ken Yamada et al.   ACS Chemical Biology

Probing an Allosteric Pocket of CDK2 with Small Molecules

(2016) Michael S. Christodoulou et al.   ChemMedChem

Expanding the Opportunities for Modulating Kinase Targets with Allosteric Approaches

(2016) Henrik Mobitz et al.   CURRENT TOPICS IN MEDICINAL CHEMISTRY

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

Structural characterization of nonactive site, TrkA-selective kinase inhibitors

(2016) Hua-Poo Su et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Discovery of a novel allosteric inhibitor-binding site in ERK5: comparison with the canonical kinase hinge ATP-binding site

(2016) Hongming Chen et al.   Acta Crystallographica Section D-Structural Biology

Covalent-Allosteric Kinase Inhibitors

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

Dynamics-Driven Allostery in Protein Kinases

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

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

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

Targeting AKT1-E17K and the PI3K/AKT Pathway with an Allosteric AKT Inhibitor, ARQ 092

(2015) Yi Yu et al.   PLoS One

Targeting Conformational Plasticity of Protein Kinases

(2014) Michael Tong et al.   ACS Chemical Biology

Selectively targeting an inactive conformation of interleukin-2-inducible T-cell kinase by allosteric inhibitors

(2014) Seungil Han et al.   BIOCHEMICAL JOURNAL

Structure-based discovery of the first allosteric inhibitors of cyclin-dependent kinase 2

(2014) Giulio Rastelli et al.   CELL CYCLE

Combined Vemurafenib and Cobimetinib in BRAF-Mutated Melanoma

(2014) James Larkin et al.   NEW ENGLAND JOURNAL OF MEDICINE

Discovery of a Type III Inhibitor of LIM Kinase 2 That Binds in a DFG-Out Conformation

(2014) Nicole C. Goodwin et al.   ACS Medicinal Chemistry Letters

The Structural Basis of ATP as an Allosteric Modulator

(2014) Shaoyong Lu et al.   PLoS Computational Biology

MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: a non-randomised, open-label phase 2 study

(2013) Paolo A Ascierto et al.   LANCET ONCOLOGY

Strategies for the Selective Regulation of Kinases with Allosteric Modulators: Exploiting Exclusive Structural Features

(2012) Zhizhou Fang et al.   ACS Chemical Biology

Structural and Energetic Basis of Allostery

(2012) Vincent J. Hilser et al.   Annual Review of Biophysics

New Directions in Targeting Protein Kinases: Focusing Upon True Allosteric and Bivalent Inhibitors

(2012) Vandana Lamba et al.   CURRENT PHARMACEUTICAL DESIGN

Discovery and characterization of novel allosteric FAK inhibitors

(2012) Misa Iwatani et al.   EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY

Approaches to discover non-ATP site kinase inhibitors

(2012) Lori Krim Gavrin et al.   MedChemComm

Novel Carboxamide-Based Allosteric MEK Inhibitors: Discovery and Optimization Efforts toward XL518 (GDC-0973)

(2012) Kenneth D. Rice et al.   ACS Medicinal Chemistry Letters

Discovery of a Potential Allosteric Ligand Binding Site in CDK2

(2011) Stephane Betzi et al.   ACS Chemical Biology

The Evolution of Protein Kinase Inhibitors from Antagonists to Agonists of Cellular Signaling

(2011) Arvin C. Dar et al.   Annual Review of Biochemistry

GSK1120212 (JTP-74057) Is an Inhibitor of MEK Activity and Activation with Favorable Pharmacokinetic Properties for Sustained In Vivo Pathway Inhibition

(2011) A. G. Gilmartin et al.   CLINICAL CANCER RESEARCH

Discovery of a Highly Potent and Selective MEK Inhibitor: GSK1120212 (JTP-74057 DMSO Solvate)

(2011) Hiroyuki Abe et al.   ACS Medicinal Chemistry Letters

ARQ 197, a Novel and Selective Inhibitor of the Human c-Met Receptor Tyrosine Kinase with Antitumor Activity

(2010) N. Munshi et al.   MOLECULAR CANCER THERAPEUTICS

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

(2010) Jianming Zhang et al.   NATURE

An Ensemble View of Allostery

(2010) V. J. Hilser   SCIENCE

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

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

The discovery of the benzhydroxamate MEK inhibitors CI-1040 and PD 0325901

(2008) Stephen D. Barrett et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Development of thioquinazolinones, allosteric Chk1 kinase inhibitors

(2008) Antonella Converso et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS