Twenty years on: the impact of fragments on drug discovery

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

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An inhibitor of Bcl-2 family proteins induces regression of solid tumours

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

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

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Discovering High-Affinity Ligands for Proteins: SAR by NMR

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Crystal structure of the human β2 adrenergic G-protein-coupled receptor

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Ligand efficiency: a useful metric for lead selection

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

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A ‘Rule of Three’ for fragment-based lead discovery?

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

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Impact of high-throughput screening in biomedical research

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The role of ligand efficiency metrics in drug discovery

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Chemistry: Chemical con artists foil drug discovery

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A Common Mechanism Underlying Promiscuous Inhibitors from Virtual and High-Throughput Screening

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On the attribution and additivity of binding energies

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Molecular Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery

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Vemurafenib: the first drug approved for BRAF-mutant cancer

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Molecular Interaction Studies Using Microscale Thermophoresis

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Selective inhibition of oncogenic KRAS output with small molecules targeting the inactive state

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Fragment-Based Drug Discovery

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

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Druggability Indices for Protein Targets Derived from NMR-Based Screening Data

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

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Identification and Prediction of Promiscuous Aggregating Inhibitors among Known Drugs

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An Aggregation Advisor for Ligand Discovery

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Fragment-Based Lead Discovery Using X-ray Crystallography

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Molecular obesity, potency and other addictions in drug discovery

Hann, M. M. (2011) · MedChemComm · doi:10.1039/c1md00017a · Cited by 368

Privileged Molecules for Protein Binding Identified from NMR-Based Screening

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High-throughput assays for promiscuous inhibitors

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

Jhoti, H., Williams, G., Rees, D. C., & Murray, C. W. (2013) · Nature Reviews Drug Discovery · doi:10.1038/nrd3926-c1 · Cited by 330

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

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Discovery of Potent Nonpeptide Inhibitors of Stromelysin Using SAR by NMR

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

Friberg, A., Vigil, D., Zhao, B., Daniels, R. N., Burke, J. P., García-Barrantes, P. M., Camper, D. V., Chauder, B. A., Lee, T., Olejniczak, E. T., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm301448p · Cited by 318

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

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Fluorine-NMR Experiments for High-Throughput Screening: Theoretical Aspects, Practical Considerations, and Range of Applicability

Dalvit, C., Fagerness, P. E., Hadden, D. T. A., Sarver, R. W., & Stockman, B. J. (2003) · Journal of the American Chemical Society · doi:10.1021/ja034646d · Cited by 251

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

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Design Principles for Fragment Libraries: Maximizing the Value of Learnings from Pharma Fragment-Based Drug Discovery (FBDD) Programs for Use in Academia

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Experiences in fragment-based drug discovery

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ALARM NMR: A Rapid and Robust Experimental Method To Detect Reactive False Positives in Biochemical Screens

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NMR screening techniques in drug discovery and drug design

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Fragment-based drug discovery using NMR spectroscopy

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NMR-Based Screening of Proteins Containing 13C-Labeled Methyl Groups

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Observations on Screening-Based Research and Some Concerning Trends in the Literature

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

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

Leach, A. R., & Hann, M. M. (2011) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2011.05.008 · Cited by 172

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

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Fragment-based screening using X-ray crystallography and NMR spectroscopy

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Efficient exploration of chemical space by fragment-based screening

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Fragment-based hit identification: thinking in 3D

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Biophysical Fragment Screening of the β 1 -Adrenergic Receptor: Identification of High Affinity Arylpiperazine Leads Using Structure-Based Drug Design

Christopher, J. A., Brown, J. D., Dore, A. S., Errey, J. C., Koglin, M., Marshall, F. H., Myszka, D. G., Rich, R. L., Tate, C. G., Tehan, B. G., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm400140q · Cited by 163

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

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

Davis, B. J., & Erlanson, D. A. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.03.028 · Cited by 145

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

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Detection of secondary binding sites in proteins using fragment screening

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From Experimental Design to Validated Hits

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

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

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An Integrated Approach to Fragment-Based Lead Generation:Philosophy, Strategy and Case Studies from AstraZenecas Drug Discovery Programmes

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

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

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Discovery of Leukotriene A4 Hydrolase Inhibitors Using Metabolomics Biased Fragment Crystallography

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

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Discovery of an allosteric mechanism for the regulation of HCV NS3 protein function

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

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

Caldwell, J., Davies, T. G., Donald, A., McHardy, T., Rowlands, M., Aherne, G. W., Hunter, L. K., Taylor, K., Ruddle, R. R., Raynaud, F. I., et al. (2008) · Journal of Medicinal Chemistry · doi:10.1021/jm701437d · Cited by 103

Compound Design by Fragment‐Linking

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

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Antibacterial alkoxybenzamide inhibitors of the essential bacterial cell division protein FtsZ

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

Devine, S. M., Mulcair, M. D., Debono, C. O., Leung, E. W. W., Nissink, J. W. M., Lim, S. S., Chandrashekaran, I. R., Vazirani, M., Mohanty, B., Simpson, J. S., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/jm501402x · Cited by 91

Expanding medicinal chemistry space

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

Murray, J. B., Roughley, S. D., Matassova, N., & Brough, P. A. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401848a · Cited by 86

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

Petros, A. M., Swann, S. L., Song, D., Swinger, K. K., Park, C., Zhang, H., Wendt, M. D., Kunzer, A. R., Souers, A. J., & Sun, C. C. (2014) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2014.02.010 · Cited by 83

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

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Parallel Screening of Low Molecular Weight Fragment Libraries: Do Differences in Methodology Affect Hit Identification?

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

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

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Selectivity of Kinase Inhibitor Fragments

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Tactics in Contemporary Drug Design

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Fragment‐based Drug Discovery Lessons and Outlook

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

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Ligand-Orientation Based Fragment Selection in STD NMR Screening

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

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NMR-Based Quality Control Approach for the Identification of False Positives and False Negatives in High Throughput Screening

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Practical Aspects of NMR-Based Fragment Screening

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Design and Generation of Highly Diverse Fluorinated Fragment Libraries and their Efficient Screening with Improved 19F NMR Methodology

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

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

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Docking and Linking of Fragments To Discover Jumonji Histone Demethylase Inhibitors

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Integrating biophysics with HTS-driven drug discovery projects

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Integrating Surface Plasmon Resonance Biosensor-Based Interaction Kinetic Analyses into the Lead Discovery and Optimization Process

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