Twenty years on: the impact of fragments on drug discovery

Six Biophysical Screening Methods Miss a Large Proportion of Crystallographically Discovered Fragment Hits: A Case Study

(2016) Johannes Schiebel et al.   ACS Chemical Biology

Integrating biophysics with HTS-driven drug discovery projects

(2016) Rutger H.A. Folmer   DRUG DISCOVERY TODAY

Monoacidic Inhibitors of the Kelch-like ECH-Associated Protein 1: Nuclear Factor Erythroid 2-Related Factor 2 (KEAP1:NRF2) Protein–Protein Interaction with High Cell Potency Identified by Fragment-Based Discovery

(2016) Thomas G. Davies et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design and synthesis of dihydroisoquinolones for fragment-based drug discovery (FBDD)

(2016) Nick Palmer et al.   ORGANIC & BIOMOLECULAR CHEMISTRY

Selective Inhibition of Oncogenic KRAS Output with Small Molecules Targeting the Inactive State

(2016) M. P. Patricelli et al.   Cancer Discovery

Rapid experimental SAD phasing and hot-spot identification with halogenated fragments

(2016) Joseph D. Bauman et al.   IUCrJ

Opportunity Knocks: Organic Chemistry for Fragment-Based Drug Discovery (FBDD)

(2015) Christopher W. Murray et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Cell-based and virtual fragment screening for adrenergic α2C receptor agonists

(2015) Edit Szőllősi et al.   BIOORGANIC & MEDICINAL CHEMISTRY

One Question, Multiple Answers: Biochemical and Biophysical Screening Methods Retrieve Deviating Fragment Hit Lists

(2015) Johannes Schiebel et al.   ChemMedChem

Docking and Linking of Fragments To Discover Jumonji Histone Demethylase Inhibitors

(2015) Magdalena Korczynska et al.   JOURNAL OF MEDICINAL CHEMISTRY

Small Molecule Binding Sites on the Ras:SOS Complex Can Be Exploited for Inhibition of Ras Activation

(2015) Jon J. G. Winter et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Tricyclic Indoles That Potently Inhibit Mcl-1 Using Fragment-Based Methods and Structure-Based Design

(2015) Jason P. Burke et al.   JOURNAL OF MEDICINAL CHEMISTRY

Promiscuous 2-Aminothiazoles (PrATs): A Frequent Hitting Scaffold

(2015) Shane M. Devine et al.   JOURNAL OF MEDICINAL CHEMISTRY

Ligand-Orientation Based Fragment Selection in STD NMR Screening

(2015) Olivier Cala et al.   JOURNAL OF MEDICINAL CHEMISTRY

An Aggregation Advisor for Ligand Discovery

(2015) John J. Irwin et al.   JOURNAL OF MEDICINAL CHEMISTRY

Detection of secondary binding sites in proteins using fragment screening

(2015) R. Frederick Ludlow et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Ligand deconstruction: Why some fragment binding positions are conserved and others are not

(2015) Dima Kozakov et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

A binding hotspot inTrypanosoma cruzihistidyl-tRNA synthetase revealed by fragment-based crystallographic cocktail screens

(2015) Cho Yeow Koh et al.   ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY

Discovery of Selective Small-Molecule Activators of a Bacterial Glycoside Hydrolase

(2014) John F. Darby et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Fragment-based discovery of potent inhibitors of the anti-apoptotic MCL-1 protein

(2014) Andrew M. Petros et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Off-Rate Screening (ORS) By Surface Plasmon Resonance. An Efficient Method to Kinetically Sample Hit to Lead Chemical Space from Unpurified Reaction Products

(2014) James B. Murray et al.   JOURNAL OF MEDICINAL CHEMISTRY

Chemistry: Chemical con artists foil drug discovery

(2014) Jonathan Baell et al.   NATURE

The role of ligand efficiency metrics in drug discovery

(2014) Andrew L. Hopkins et al.   NATURE REVIEWS DRUG DISCOVERY

Efficient exploration of chemical space by fragment-based screening

(2014) Richard J. Hall et al.   PROGRESS IN BIOPHYSICS & MOLECULAR BIOLOGY

Fragment Screening by Weak Affinity Chromatography: Comparison with Established Techniques for Screening against HSP90

(2013) Elinor Meiby et al.   ANALYTICAL CHEMISTRY

Design and Evaluation of the Performance of an NMR Screening Fragment Library

(2013) Bradley C. Doak et al.   AUSTRALIAN JOURNAL OF CHEMISTRY

Learning from our mistakes: The ‘unknown knowns’ in fragment screening

(2013) Ben J. Davis et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Design and Generation of Highly Diverse Fluorinated Fragment Libraries and their Efficient Screening with Improved19F NMR Methodology

(2013) Anna Vulpetti et al.   ChemMedChem

Tailoring Small Molecules for an Allosteric Site on Procaspase-6

(2013) Jeremy Murray et al.   ChemMedChem

Fragment-based hit identification: thinking in 3D

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

Fragment-based drug discovery using NMR spectroscopy

(2013) Mary J. Harner et al.   JOURNAL OF BIOMOLECULAR NMR

A Novel Class of Oral Direct Renin Inhibitors: Highly Potent 3,5-Disubstituted Piperidines Bearing a Tricyclic P3–P1 Pharmacophore

(2013) Nils Ostermann et al.   JOURNAL OF MEDICINAL CHEMISTRY

Detecting Allosteric Sites of HIV-1 Reverse Transcriptase by X-ray Crystallographic Fragment Screening

(2013) Joseph D. Bauman et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of 4-Amino-N-[(1S)-1-(4-chlorophenyl)-3-hydroxypropyl]-1-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)piperidine-4-carboxamide (AZD5363), an Orally Bioavailable, Potent Inhibitor of Akt Kinases

(2013) Matt Addie et al.   JOURNAL OF MEDICINAL CHEMISTRY

Biophysical Fragment Screening of the β1-Adrenergic Receptor: Identification of High Affinity Arylpiperazine Leads Using Structure-Based Drug Design

(2013) John A. Christopher et al.   JOURNAL OF MEDICINAL CHEMISTRY

How Are Fragments Optimized? A Retrospective Analysis of 145 Fragment Optimizations

(2013) György G. Ferenczy et al.   JOURNAL OF MEDICINAL CHEMISTRY

Discovery of Potent, Selective Chymase Inhibitors via Fragment Linking Strategies

(2013) Steven J. Taylor et al.   JOURNAL OF MEDICINAL CHEMISTRY

K-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions

(2013) Jonathan M. Ostrem 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

A three-stage biophysical screening cascade for fragment-based drug discovery

(2013) Ellene H Mashalidis et al.   Nature Protocols

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

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

Fragment growing to retain or alter the selectivity of anchored kinase hinge-binding fragments

(2013) Charlotte E. Allen et al.   MedChemComm

Discovery of Small Molecules that Bind to K-Ras and Inhibit Sos-Mediated Activation

(2012) Qi Sun et al.   ANGEWANDTE CHEMIE-INTERNATIONAL EDITION

Small and colorful stones make beautiful mosaics: fragment-based chemogenomics

(2012) Chris de Graaf et al.   DRUG DISCOVERY TODAY

Expanding medicinal chemistry space

(2012) Andy Barker et al.   DRUG DISCOVERY TODAY

Enumeration of 166 Billion Organic Small Molecules in the Chemical Universe Database GDB-17

(2012) Lars Ruddigkeit et al.   Journal of Chemical Information and Modeling

Discovery of Potent Myeloid Cell Leukemia 1 (Mcl-1) Inhibitors Using Fragment-Based Methods and Structure-Based Design

(2012) Anders Friberg et al.   JOURNAL OF MEDICINAL CHEMISTRY

Design and Synthesis of Novel Lactate Dehydrogenase A Inhibitors by Fragment-Based Lead Generation

(2012) Richard A. Ward et al.   JOURNAL OF MEDICINAL CHEMISTRY

Natural-product-derived fragments for fragment-based ligand discovery

(2012) Björn Over et al.   Nature Chemistry

Vemurafenib: the first drug approved for BRAF-mutant cancer

(2012) Gideon Bollag et al.   NATURE REVIEWS DRUG DISCOVERY

Small-molecule ligands bind to a distinct pocket in Ras and inhibit SOS-mediated nucleotide exchange activity

(2012) T. Maurer et al.   PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA

Experiences in fragment-based drug discovery

(2012) Christopher W. Murray et al.   TRENDS IN PHARMACOLOGICAL SCIENCES

Molecular Interaction Studies Using Microscale Thermophoresis

(2011) Moran Jerabek-Willemsen et al.   ASSAY AND DRUG DEVELOPMENT TECHNOLOGIES

Molecular complexity and fragment-based drug discovery: ten years on

(2011) Andrew R Leach et al.   CURRENT OPINION IN CHEMICAL BIOLOGY

Design of a multi-purpose fragment screening library using molecular complexity and orthogonal diversity metrics

(2011) Wan F. Lau et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

Selectivity of Kinase Inhibitor Fragments

(2011) Paul Bamborough et al.   JOURNAL OF MEDICINAL CHEMISTRY

Compound Design by Fragment-Linking

(2011) Osamu Ichihara et al.   Molecular Informatics

The influence of the 'organizational factor' on compound quality in drug discovery

(2011) Paul D. Leeson et al.   NATURE REVIEWS DRUG DISCOVERY

Impact of high-throughput screening in biomedical research

(2011) Ricardo Macarron et al.   NATURE REVIEWS DRUG DISCOVERY

Molecular obesity, potency and other addictions in drug discovery

(2011) Michael M. Hann   MedChemComm

High concentration electrophysiology-based fragment screen: Discovery of novel acid-sensing ion channel 3 (ASIC3) inhibitors

(2010) Scott E. Wolkenberg et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Observations on screening-based research and some concerning trends in the literature

(2010) Jonathan B Baell   Future Medicinal Chemistry

Entropic Contribution to the Linking Coefficient in Fragment Based Drug Design: A Case Study

(2010) Valentina Borsi 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

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

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

(2009) Mark Whittaker   DRUG DISCOVERY TODAY

Kinase-targeted libraries: The design and synthesis of novel, potent, and selective kinase inhibitors

(2009) Irini Akritopoulou-Zanze et al.   DRUG DISCOVERY TODAY

Integrating surface plasmon resonance biosensor-based interaction kinetic analyses into the lead discovery and optimization process

(2009) U Helena Danielson   Future Medicinal Chemistry

Lessons for fragment library design: analysis of output from multiple screening campaigns

(2009) I-Jen Chen et al.   JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN

Discovery of Leukotriene A4 Hydrolase Inhibitors Using Metabolomics Biased Fragment Crystallography†

(2009) Douglas R. Davies et al.   JOURNAL OF MEDICINAL CHEMISTRY

Antibacterial alkoxybenzamide inhibitors of the essential bacterial cell division protein FtsZ

(2008) Lloyd G. Czaplewski et al.   BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

Identification of 4-(4-Aminopiperidin-1-yl)-7H-pyrrolo[2,3-d]pyrimidines as Selective Inhibitors of Protein Kinase B through Fragment Elaboration

(2008) John J. Caldwell et al.   JOURNAL OF MEDICINAL CHEMISTRY

Structure of a β1-adrenergic G-protein-coupled receptor

(2008) Tony Warne et al.   NATURE