Small molecules, big targets: drug discovery faces the protein–protein interaction challenge

Small-molecule inhibitors of the Myc oncoprotein

(2015) Steven Fletcher et al.   Biochimica et Biophysica Acta-Gene Regulatory Mechanisms

Flexibility and small pockets at protein–protein interfaces: New insights into druggability

(2015) Harry Jubb et al.   PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY

Rational design of protein–protein interaction inhibitors

(2015) Didier Rognan   MedChemComm

Towards understanding cell penetration by stapled peptides

(2015) Qian Chu et al.   MedChemComm

Small-Molecule Inhibitors of Protein-Protein Interactions: Progressing toward the Reality

(2014) Michelle R. Arkin et al.   CHEMISTRY & BIOLOGY

Small-Molecule Inhibitors That Target Protein-Protein Interactions in the RAD51 Family of Recombinases

(2014) Duncan E. Scott et al.   ChemMedChem

Structure-based design of small-molecule protein–protein interaction modulators: the story so far

(2014) Federico Falchi et al.   Future Medicinal Chemistry

The Use of Chlorobenzene as a Probe Molecule in Molecular Dynamics Simulations

(2014) Yaw Sing Tan et al.   Journal of Chemical Information and Modeling

Rapid Identification of Keap1–Nrf2 Small-Molecule Inhibitors through Structure-Based Virtual Screening and Hit-Based Substructure Search

(2014) Chunlin Zhuang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Small-Molecule Inhibitors of the MDM2–p53 Protein–Protein Interaction (MDM2 Inhibitors) in Clinical Trials for Cancer Treatment

(2014) Yujun Zhao et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

Hydrocarbon-Stapled Peptides: Principles, Practice, and Progress

(2014) Loren D. Walensky et al.   JOURNAL OF MEDICINAL CHEMISTRY

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

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

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

Using a Fragment-Based Approach To Target Protein-Protein Interactions

(2013) Duncan E. Scott et al.   CHEMBIOCHEM

Fragment-based hit identification: thinking in 3D

(2013) Andrew D. Morley et al.   DRUG DISCOVERY TODAY

Design and Synthesis of a Prototype Scaffold for Five-Residue α-Helix Mimetics

(2013) Andrew R. Bayly et al.   EUROPEAN JOURNAL OF ORGANIC CHEMISTRY

Discovery of Epigenetic Regulator I-BET762: Lead Optimization to Afford a Clinical Candidate Inhibitor of the BET Bromodomains

(2013) Olivier Mirguet et al.   JOURNAL OF MEDICINAL CHEMISTRY

Optimization of Benzodiazepinones as Selective Inhibitors of the X-Linked Inhibitor of Apoptosis Protein (XIAP) Second Baculovirus IAP Repeat (BIR2) Domain

(2013) Robert F. Kester et al.   JOURNAL OF MEDICINAL CHEMISTRY

Benzazepinones and Benzoxazepinones as Antagonists of Inhibitor of Apoptosis Proteins (IAPs) Selective for the Second Baculovirus IAP Repeat (BIR2) Domain

(2013) Andrew F. Donnell et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Potent Mcl-1/Bcl-xL Dual Inhibitors by Using a Hybridization Strategy Based on Structural Analysis of Target Proteins

(2013) Yuta Tanaka et al.   JOURNAL OF MEDICINAL CHEMISTRY

Small molecule inhibition of the KRAS–PDEδ interaction impairs oncogenic KRAS signalling

(2013) Gunther Zimmermann et al.   NATURE

ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets

(2013) Andrew J Souers et al.   NATURE MEDICINE

The 'rule of three' for fragment-based drug discovery: where are we now?

(2013) Harren Jhoti et al.   NATURE REVIEWS DRUG DISCOVERY

Peptide inhibitors of the Keap1–Nrf2 protein–protein interaction with improved binding and cellular activity

(2013) Rowena Hancock et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Predicting where Small Molecules Bind at Protein-Protein Interfaces

(2013) Peter Walter et al.   PLoS One

Diaryl- and triaryl-pyrrole derivatives: inhibitors of the MDM2–p53 and MDMX–p53 protein–protein interactions

(2013) Tim J. Blackburn et al.   MedChemComm

Novel protein–protein interaction inhibitor of Nrf2–Keap1 discovered by structure-based virtual screening

(2013) Hao-Peng Sun et al.   MedChemComm

Deconstruction of a Nutlin: Dissecting the Binding Determinants of a Potent Protein–Protein Interaction Inhibitor

(2013) David C. Fry et al.   ACS Medicinal Chemistry Letters

Druggable Protein Interaction Sites Are More Predisposed to Surface Pocket Formation than the Rest of the Protein Surface

(2013) David K. Johnson et al.   PLoS Computational Biology

Identification of a phenylacylsulfonamide series of dual Bcl-2/Bcl-xL antagonists

(2012) Heidi L. Perez et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Histone Recognition and Large-Scale Structural Analysis of the Human Bromodomain Family

(2012) Panagis Filippakopoulos et al.   CELL

The Future of Peptide-based Drugs

(2012) David J. Craik et al.   Chemical Biology & Drug Design

Dissecting Fragment-Based Lead Discovery at the von Hippel-Lindau Protein:Hypoxia Inducible Factor 1α Protein-Protein Interface

(2012) Inge Van Molle et al.   CHEMISTRY & BIOLOGY

Computational Drug Design Targeting Protein-Protein Interactions

(2012) Rachelle J. Bienstock   CURRENT PHARMACEUTICAL DESIGN

Features of protein–protein interactions that translate into potent inhibitors: topology, surface area and affinity

(2012) Matthew C. Smith et al.   EXPERT REVIEWS IN MOLECULAR MEDICINE

Design of Bcl-2 and Bcl-xL Inhibitors with Subnanomolar Binding Affinities Based upon a New Scaffold

(2012) Haibin Zhou et al.   JOURNAL OF MEDICINAL CHEMISTRY

High-Affinity, Small-Molecule Peptidomimetic Inhibitors of MLL1/WDR5 Protein–Protein Interaction

(2012) Hacer Karatas et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Structure-based prediction of protein–protein interactions on a genome-wide scale

(2012) Qiangfeng Cliff Zhang et al.   NATURE

Epigenetic protein families: a new frontier for drug discovery

(2012) Cheryl H. Arrowsmith et al.   NATURE REVIEWS DRUG DISCOVERY

2P2Idb: a structural database dedicated to orthosteric modulation of protein–protein interactions

(2012) Marie Jeanne Basse et al.   NUCLEIC ACIDS RESEARCH

Small Molecule Inhibitors of the LEDGF Site of Human Immunodeficiency Virus Integrase Identified by Fragment Screening and Structure Based Design

(2012) Thomas S. Peat et al.   PLoS One

Biophysical and computational fragment-based approaches to targeting protein–protein interactions: applications in structure-guided drug discovery

(2012) Anja Winter et al.   QUARTERLY REVIEWS OF BIOPHYSICS

From Crystal Packing to Molecular Recognition: Prediction and Discovery of a Binding Site on the Surface of Polo-Like Kinase 1

(2011) Paweł Śledź et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Dr. PIAS: an integrative system for assessing the druggability of protein-protein interactions

(2011) Nobuyoshi Sugaya et al.   BMC BIOINFORMATICS

Comprehensive, atomic-level characterization of structurally characterized protein-protein interactions: the PICCOLO database

(2011) George R Bickerton et al.   BMC BIOINFORMATICS

Kinetic Analyses of Keap1-Nrf2 Interaction and Determination of the Minimal Nrf2 Peptide Sequence Required for Keap1 Binding Using Surface Plasmon Resonance

(2011) Yu Chen et al.   Chemical Biology & Drug Design

Chemical and structural lessons from recent successes in protein–protein interaction inhibition (2P2I)

(2011) Xavier Morelli et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Peptide inhibitors of the Keap1–Nrf2 protein–protein interaction

(2011) Rowena Hancock et al.   FREE RADICAL BIOLOGY AND MEDICINE

Emerging role of surface plasmon resonance in fragment-based drug discovery

(2011) Iva Navratilova et al.   Future Medicinal Chemistry

Thermodynamic Properties of Water Molecules at a Protein–Protein Interaction Surface

(2011) David J. Huggins et al.   Journal of Chemical Theory and Computation

A Potent and Orally Active Antagonist (SM-406/AT-406) of Multiple Inhibitor of Apoptosis Proteins (IAPs) in Clinical Development for Cancer Treatment

(2011) Qian Cai et al.   JOURNAL OF MEDICINAL CHEMISTRY

Screening Multicomponent Reactions for X-Linked Inhibitor of Apoptosis-Baculoviral Inhibitor of Apoptosis Protein Repeats Domain Binder

(2011) Ilaria Monfardini et al.   JOURNAL OF MEDICINAL CHEMISTRY

Quinazoline Sulfonamides as Dual Binders of the Proteins B-Cell Lymphoma 2 and B-Cell Lymphoma Extra Long with Potent Proapoptotic Cell-Based Activity

(2011) Brad E. Sleebs et al.   JOURNAL OF MEDICINAL CHEMISTRY

Compound Design by Fragment-Linking

(2011) Osamu Ichihara et al.   Molecular Informatics

Inhibition of bromodomain-mediated protein–protein interactions as a novel therapeutic strategy

(2011) Silviya D. Furdas et al.   MedChemComm

Systematic Analysis of Helical Protein Interfaces Reveals Targets for Synthetic Inhibitors

(2010) Andrea L. Jochim et al.   ACS Chemical Biology

Evidence that inhibition of BAX activation by BCL-2 involves its tight and preferential interaction with the BH3 domain of BAX

(2010) Bonsu Ku et al.   CELL RESEARCH

Update 1 of: Beta-Strand Mimetics

(2010) Wendy A. Loughlin et al.   CHEMICAL REVIEWS

Drugging challenging targets using fragment-based approaches

(2010) Anthony G Coyne et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Targeting the BH3 Domain Mediated Protein−Protein Interaction of Bcl-xL through Virtual Screening

(2010) Prasenjit Mukherjee et al.   Journal of Chemical Information and Modeling

Fragment-Based Deconstruction of Bcl-xLInhibitors

(2010) Sarah Barelier et al.   JOURNAL OF MEDICINAL CHEMISTRY

New Substructure Filters for Removal of Pan Assay Interference Compounds (PAINS) from Screening Libraries and for Their Exclusion in Bioassays

(2010) Jonathan B. Baell et al.   JOURNAL OF MEDICINAL CHEMISTRY

Selective inhibition of BET bromodomains

(2010) Panagis Filippakopoulos et al.   NATURE

Magic bullets in nature's arsenal

(2010) Joshua A Kritzer   Nature Chemical Biology

Rational design of small-molecule inhibitors of the LEDGF/p75-integrase interaction and HIV replication

(2010) Frauke Christ et al.   Nature Chemical Biology

The MCL-1 BH3 helix is an exclusive MCL-1 inhibitor and apoptosis sensitizer

(2010) Michelle L Stewart et al.   Nature Chemical Biology

Integrins as therapeutic targets: lessons and opportunities

(2010) Dermot Cox et al.   NATURE REVIEWS DRUG DISCOVERY

The STRING database in 2011: functional interaction networks of proteins, globally integrated and scored

(2010) D. Szklarczyk et al.   NUCLEIC ACIDS RESEARCH

ANCHOR: a web server and database for analysis of protein-protein interaction binding pockets for drug discovery

(2010) L. M. C. Meireles et al.   NUCLEIC ACIDS RESEARCH

The Overlap of Small Molecule and Protein Binding Sites within Families of Protein Structures

(2010) Fred P. Davis et al.   PLoS Computational Biology

High-Resolution Structural Characterization of a Helical α/β-Peptide Foldamer Bound to the Anti-Apoptotic Protein Bcl-xL

(2009) Erinna F. Lee et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Atomic Interactions and Profile of Small Molecules Disrupting Protein-Protein Interfaces: the TIMBAL Database

(2009) Alícia P. Higueruelo et al.   Chemical Biology & Drug Design

Picking up the pieces with FBDD or FADD: invest early for future success

(2009) Mark Whittaker   DRUG DISCOVERY TODAY

Conformational Changes in Bcl-2 Pro-survival Proteins Determine Their Capacity to Bind Ligands

(2009) Erinna F. Lee et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Discovery and Optimization of Chromenotriazolopyrimidines as Potent Inhibitors of the Mouse Double Minute 2−Tumor Protein 53 Protein−Protein Interaction

(2009) John G. Allen et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design, Synthesis, and Evaluation of an α-Helix Mimetic Library Targeting Protein−Protein Interactions

(2009) Alex Shaginian et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

Multiple Independent Binding Sites for Small-Molecule Inhibitors on the Oncoprotein c-Myc

(2009) Dalia I. Hammoudeh et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY

β-Peptidic Peptidomimetics

(2008) Dieter Seebach et al.   ACCOUNTS OF CHEMICAL RESEARCH

Designing Smac-mimetics as antagonists of XIAP, cIAP1, and cIAP2

(2008) Federica Cossu et al.   BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS

ABT-263: A Potent and Orally Bioavailable Bcl-2 Family Inhibitor

(2008) C. Tse et al.   CANCER RESEARCH

Bcl-2 inhibitors: small molecules with a big impact on cancer therapy

(2008) M Vogler et al.   CELL DEATH AND DIFFERENTIATION

Principles of Protein−Protein Interactions: What are the Preferred Ways For Proteins To Interact?

(2008) Ozlem Keskin et al.   CHEMICAL REVIEWS

Structural Rationale for the Coupled Binding and Unfolding of the c-Myc Oncoprotein by Small Molecules

(2008) Ariele Viacava Follis et al.   CHEMISTRY & BIOLOGY

Contemporary strategies for the stabilization of peptides in the α-helical conformation

(2008) Laura K Henchey et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Predicting druggable binding sites at the protein–protein interface

(2008) Jonathan C. Fuller et al.   DRUG DISCOVERY TODAY

Structure of WDR5 Bound to Mixed Lineage Leukemia Protein-1 Peptide

(2008) Anamika Patel et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

A Conserved Arginine-containing Motif Crucial for the Assembly and Enzymatic Activity of the Mixed Lineage Leukemia Protein-1 Core Complex

(2008) Anamika Patel et al.   JOURNAL OF BIOLOGICAL CHEMISTRY

Fragment-Based Design of Small Molecule X-Linked Inhibitor of Apoptosis Protein Inhibitors

(2008) Jui-Wen Huang et al.   JOURNAL OF MEDICINAL CHEMISTRY

Atomic Structure of a Short α-Helix Stabilized by a Main Chain Hydrogen-Bond Surrogate

(2008) Jie Liu et al.   JOURNAL OF THE AMERICAN CHEMICAL SOCIETY