Cited by 223Computational Drug Discovery MethodsChemical Synthesis and AnalysisReceptor Mechanisms and Signaling

The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.

Ligand efficiency and fragment-based drug discovery

Bembenek, Scott D., Tounge, Brett A., Reynolds, Charles H.·2009·Drug Discovery Today

DOI 10.1016/j.drudis.2008.11.007

Open this paper in CoChat — free account

Abstract

The use of fragment-based drug discovery (FBDD) has increased in recent years since it is more likely to produce a better optimized compound of lower molecular weight. Ligand efficiency (LE) has become important for assessing fragments, HTS hits, and resulting optimized ligands. LE is useful for comparing ligands of equal molecular weight, but is ineffective for comparisons of ligands of differing molecular weight. LE has a strong dependence on molecular size, which has led us to develop a size-independent efficiency score termed fit quality. Evaluating FBDD examples from the literature using LE and fit quality, we find that, in general, the LEs of starting fragments are greater than those of larger, more elaborated, structures. Fit quality scores, however, tend to improve upon optimization of the fragments.

Integrity signals

Registry

Crossref · 10.1016/j.drudis.2008.11.007

Cites

23 of 23 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

This paper’s full text isn’t openly available, so its claims and self-check weren’t run. The registry and citation checks still apply.

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

Lead- and drug-like compounds: the rule-of-five revolution
Lipinski, C. A. (2004) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2004.11.007 · Cited by 6,455
Discovering High-Affinity Ligands for Proteins: SAR by NMR
Shuker, S. B., Hajduk, P. J., Meadows, R. P., & Fesik, S. W. (1996) · Science · doi:10.1126/science.274.5292.1531 · Cited by 2,045
Ligand efficiency: a useful metric for lead selection
Hopkins, A. L., Groom, C. R., & Alex, A. (2004) · Drug Discovery Today · doi:10.1016/s1359-6446(04)03069-7 · Cited by 1,895
Avidin
Green, N. M. (1975) · Advances in protein chemistry · doi:10.1016/s0065-3233(08)60411-8 · Cited by 1,472
A decade of fragment-based drug design: strategic advances and lessons learned
Hajduk, P., & Greer, J. (2007) · Nature reviews. Drug discovery · doi:10.1038/nrd2220 · Cited by 1,004
On the attribution and additivity of binding energies
Jencks, W. P. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.7.4046 · Cited by 938
Molecular Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery
Hann, M. M., Leach, A. R., & Harper, G. (2001) · Journal of Chemical Information and Computer Sciences · doi:10.1021/ci000403i · Cited by 904
The maximal affinity of ligands
Kuntz, I. D., Chen, K., Sharp, K. A., & Kollman, P. A. (1999) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.96.18.9997 · Cited by 859
Fragment-based lead discovery
Rees, D. C., Congreve, M., Murray, C. W., & Carr, R. A. E. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1467 · Cited by 812
Fragment-Based Drug Discovery
Erlanson, D. A., McDowell, R. S., & O'Brien, T. (2004) · Journal of Medicinal Chemistry · doi:10.1021/jm040031v · Cited by 645

Show all 23 references

Sorted by citations

The ErbB/HER family of protein-tyrosine kinases and cancer
Roskoski, R. J. (2013) · Pharmacological Research · doi:10.1016/j.phrs.2013.11.002 · Cited by 1,408
Improving Drug Candidates by Design: A Focus on Physicochemical Properties As a Means of Improving Compound Disposition and Safety
Meanwell, N. A. (2011) · Chemical Research in Toxicology · doi:10.1021/tx200211v · Cited by 639
Two Decades under the Influence of the Rule of Five and the Changing Properties of Approved Oral Drugs
Shultz, M. D. (2018) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.8b00686 · Cited by 466
Ligand and Target Discovery by Fragment-Based Screening in Human Cells
Parker, C. G., Galmozzi, A., Wang, Y., Correia, B. E., Sasaki, K., Joslyn, C. M., Kim, A. S., Cavallaro, C. L., Lawrence, R. M., Johnson, S. R., et al. (2017) · Cell · doi:10.1016/j.cell.2016.12.029 · Cited by 439
What Do Medicinal Chemists Actually Make? A 50-Year Retrospective
Walters, W. P., Green, J., Weiss, J. R., & Murcko, M. A. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm200504p · Cited by 395
Structure-based drug design to augment hit discovery
Kalyaanamoorthy, S., & Chen, Y. P. (2011) · Drug Discovery Today · doi:10.1016/j.drudis.2011.07.006 · Cited by 311
Introduction to Fragment-Based Drug Discovery
Erlanson, D. A. (2011) · Topics in current chemistry · doi:10.1007/128_2011_180 · Cited by 268
Ligand efficiency as a guide in fragment hit selection and optimization
Schultes, S., de Graaf, C., Haaksma, E. E. J., de Esch, I. J. P., Leurs, R., & Krämer, O. (2010) · Drug Discovery Today Technologies · doi:10.1016/j.ddtec.2010.11.003 · Cited by 259
Chemical and structural lessons from recent successes in protein–protein interaction inhibition (2P2I)
Morelli, X., Bourgeas, R., & Roche, P. (2011) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2011.05.024 · Cited by 223
Comparative Assessment of Scoring Functions on an Updated Benchmark: 1. Compilation of the Test Set
Li, Y., Liu, Z., Li, J., Han, L., Liu, J., Zhao, Z., & Wang, R. (2014) · Journal of Chemical Information and Modeling · doi:10.1021/ci500080q · Cited by 221
Molecular inflation, attrition and the rule of five
Leeson, P. D. (2016) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2016.01.018 · Cited by 184
Expedited mapping of the ligandable proteome using fully functionalized enantiomeric probe pairs
Wang, Y., Dix, M. M., Bianco, G., Remsberg, J. R., Lee, H.-Y., Kalocsay, M., Gygi, S. P., Forli, S., Vite, G., Lawrence, R. M., et al. (2019) · Nature Chemistry · doi:10.1038/s41557-019-0351-5 · Cited by 179
Setting expectations in molecular optimizations: Strengths and limitations of commonly used composite parameters
Shultz, M. D. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.08.029 · Cited by 177
Impact of Lipophilic Efficiency on Compound Quality
Tarcsay, Á., Nyíri, K., & Keserű, G. M. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201388p · Cited by 176
Design and Synthesis of Novel Lactate Dehydrogenase A Inhibitors by Fragment-Based Lead Generation
Ward, R. A., Brassington, C., Breeze, A. L., Caputo, A. T., Critchlow, S. E., Davies, G. M., Goodwin, L., Hassall, G., Greenwood, R. D. R., Holdgate, G. A., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201734r · Cited by 170
State-of-the-art strategies for targeting protein–protein interactions by small-molecule inhibitors
Sheng, C., Dong, G., Miao, Z., Zhang, W., & Wang, W. (2015) · Chemical Society Reviews · doi:10.1039/c5cs00252d · Cited by 165
De Novo Drug Design
Hartenfeller, M., & Schneider, G. (2010) · Methods in molecular biology · doi:10.1007/978-1-60761-839-3_12 · Cited by 165
Harnessing Allostery: A Novel Approach to Drug Discovery
Lu, S., Li, S., & Zhang, J. (2014) · Medicinal Research Reviews · doi:10.1002/med.21317 · Cited by 148
Thermodynamics guided lead discovery and optimization
Ferenczy, G. G., & Keserű, G. M. (2010) · Drug Discovery Today · doi:10.1016/j.drudis.2010.08.013 · Cited by 139
Ligand–receptor interaction platforms and their applications for drug discovery
Ye, F. (2012) · Expert Opinion on Drug Discovery · doi:10.1517/17460441.2012.715631 · Cited by 130
Toward the Rational Design of p53-Stabilizing Drugs: Probing the Surface of the Oncogenic Y220C Mutant
Basse, N., Kaar, J. L., Settanni, G., Joerger, A. C., Rutherford, T. J., & Fersht, A. R. (2010) · Chemistry & Biology · doi:10.1016/j.chembiol.2009.12.011 · Cited by 125
Anopheles gambiae odorant binding protein crystal complex with the synthetic repellent DEET: implications for structure-based design of novel mosquito repellents
Tsitsanou, K. E., Thireou, T. N., Drakou, C. E., Koussis, K., Keramioti, M., Leonidas, D. D., Eliopoulos, E., Iatrou, K., & Zographos, S. E. (2011) · Cellular and Molecular Life Sciences · doi:10.1007/s00018-011-0745-z · Cited by 114
4‐Acyl Pyrroles: Mimicking Acetylated Lysines in Histone Code Reading
Lucas, X., Wohlwend, D., Hügle, M. J., Schmidtkunz, K., Gerhardt, S., Schüle, R., Jung, M., Einsle, O., & Günther, S. (2013) · Angewandte Chemie International Edition · doi:10.1002/anie.201307652 · Cited by 112
Discovery, Design, and Optimization of Isoxazole Azepine BET Inhibitors
Gehling, V. S., Hewitt, M. C., Vaswani, R. G., Leblanc, Y., Côté, A., Nasveschuk, C. G., Taylor, A. M., Harmange, J.-C., Audia, J. E., Pardo, E., et al. (2013) · ACS Medicinal Chemistry Letters · doi:10.1021/ml4001485 · Cited by 107
Ligand efficiency metrics in drug discovery: the pros and cons from a practical perspective
Cavalluzzi, M. M., Mangiatordi, G. F., Nicolotti, O., & Lentini, G. (2017) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2017.1365056 · Cited by 106
Application of Fragment-Based NMR Screening, X-ray Crystallography, Structure-Based Design, and Focused Chemical Library Design to Identify Novel μM Leads for the Development of nM BACE-1 (β-Site APP Cleaving Enzyme 1) Inhibitors
Wang, Y., Strickland, C., Voigt, J. H., Kennedy, M. E., Beyer, B. M., Senior, M. M., Smith, E. M., Nechuta, T. L., Madison, V., Czarniecki, M., et al. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm901472u · Cited by 103
The thermodynamic basis for the use of lipophilic efficiency (LipE) in enthalpic optimizations
Shultz, M. D. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.08.030 · Cited by 102
Evolving molecules using multi-objective optimization: applying to ADME/Tox
Ekins, S., Honeycutt, J. D., & Metz, J. T. (2010) · Drug Discovery Today · doi:10.1016/j.drudis.2010.04.003 · Cited by 102
The impact of in silico screening in the discovery of novel and safer drug candidates
Rognan, D. (2017) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2017.02.034 · Cited by 105
A general fragment-based approach to identify and optimize bioactive ligands targeting RNA
Suresh, B. M., Li, W., Zhang, P., Wang, K. W., Yildirim, I., Parker, C. G., & Disney, M. D. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2012217117 · Cited by 103
Strategies for targeting undruggable targets
Zhang, G., Zhang, J., Gao, Y., Li, Y., & Li, Y. (2021) · Expert Opinion on Drug Discovery · doi:10.1080/17460441.2021.1969359 · Cited by 104
Allosteric modulation of AURKA kinase activity by a small-molecule inhibitor of its protein-protein interaction with TPX2
Janecek, M., Rossmann, M., Sharma, P., Emery, A., Huggins, D. J., Stockwell, S. R., Stokes, J. E., Tan, Y. S., Guarino, E., Hardwick, B. S., et al. (2016) · Scientific Reports · doi:10.1038/srep28528 · Cited by 99
The natural product eugenol is an inhibitor of the ebola virus in vitro
Lane, T., Anantpadma, M., Freundlich, J. S., Davey, R. A., Madrid, P. B., & Ekins, S. (2019) · Pharmaceutical Research · doi:10.1007/s11095-019-2629-0 · Cited by 88
Condensation-Driven Assembly of Boron-Containing Bis(Heteroaryl) Motifs Using a Linchpin Approach
Adachi, S., Liew, S. K., Lee, C. F., Lough, A. J., He, Z., Denis, J. D. S., Poda, G. I., & Yudin, A. K. (2015) · Organic Letters · doi:10.1021/acs.orglett.5b02741 · Cited by 87
Drugging challenging targets using fragment-based approaches
Coyne, A. G., Scott, D. E., & Abell, C. (2010) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2010.02.010 · Cited by 86
Detection of ligand binding hot spots on protein surfaces via fragment-based methods: application to DJ-1 and glucocerebrosidase
Landon, M. R., Lieberman, R. L., Hoang, Q. Q., Ju, S., Caaveiro, J. M. M., Orwig, S. D., Kozakov, D., Brenke, R., Chuang, G., Beglov, D., et al. (2009) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-009-9283-2 · Cited by 84
Fragment Informatics and Computational Fragment‐Based Drug Design: An Overview and Update
Sheng, C., & Zhang, W. (2013) · Medicinal Research Reviews · doi:10.1002/med.21255 · Cited by 80
N-Myristoyltransferase as a potential drug target in malaria and leishmaniasis
Tate, E. W., Bell, A., Rackham, M. D., & Wright, M. H. (2013) · Parasitology · doi:10.1017/s0031182013000450 · Cited by 80
Azetidine and Piperidine Carbamates as Efficient, Covalent Inhibitors of Monoacylglycerol Lipase
Butler, C. R., Beck, E. M., Harris, A. R., Huang, Z., McAllister, L. A., Ende, C. W. A., Fennell, K. F., Foley, T. L., Fonseca, K. R., Hawrylik, S. J., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b01531 · Cited by 76
Assessment of Dengue virus helicase and methyltransferase as targets for fragment-based drug discovery
Coutard, B., Decroly, É., Li, C., Sharff, A., Lescar, J., Bricogne, G., & Barral, K. (2014) · Antiviral Research · doi:10.1016/j.antiviral.2014.03.013 · Cited by 74
Identification of ligand efficient, fragment-like hits from an HTS library: structure-based virtual screening and docking investigations of 2H- and 3H-pyrazolo tautomers for Aurora kinase A selectivity
Sarvagalla, S., Singh, V. K., Ke, Y., Shiao, H., Lin, W., Hsieh, H., Hsu, J. T.-A., & Coumar, M. S. (2014) · Journal of Computer-Aided Molecular Design · doi:10.1007/s10822-014-9807-2 · Cited by 64
Antagonism of a zinc metalloprotease using a unique metal-chelating scaffold: tropolones as inhibitors of P. aeruginosa elastase
Fullagar, J. L., Garner, A. L., Struss, A. K., Day, J. A., Martin, D. P., Yu, J., Cai, X., Janda, K. D., & Cohen, S. M. (2013) · Chemical Communications · doi:10.1039/c3cc41191e · Cited by 64
AEG-1/MTDH/LYRIC in Liver Cancer
Sarkar, D. (2013) · Advances in cancer research · doi:10.1016/b978-0-12-401676-7.00007-3 · Cited by 61
Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum
Avery, V. M., Bashyam, S., Burrows, J. N., Duffy, S., Papadatos, G., Puthukkuti, S., Sambandan, Y., Singh, S. V., Spangenberg, T., Waterson, D., et al. (2014) · Malaria Journal · doi:10.1186/1475-2875-13-190 · Cited by 62
Application of NMR and Molecular Docking in Structure-Based Drug Discovery
Stark, J. L., & Powers, R. (2011) · Topics in current chemistry · doi:10.1007/128_2011_213 · Cited by 61
Combining NMR and X-ray Crystallography in Fragment-Based Drug Discovery: Discovery of Highly Potent and Selective BACE-1 Inhibitors
Wyss, D. F., Wang, Y., Eaton, H. L., Strickland, C., Voigt, J. H., Zhu, Z., & Stamford, A. W. (2011) · Topics in current chemistry · doi:10.1007/128_2011_183 · Cited by 59
New developments in non-quinolone-based antibiotics for the inhibiton of bacterial gyrase and topoisomerase IV
Badshah, S. L., & Ullah, A. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.04.059 · Cited by 52
Docking and Linking of Fragments To Discover Jumonji Histone Demethylase Inhibitors
Korczynska, M., Le, D. D., Younger, N. S., Gregori‐Puigjané, E., Tumber, A., Krojer, T. J., Velupillai, S., Gileadi, C., Nowak, R. P., Iwasa, E., et al. (2015) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.5b01527 · Cited by 51
Discovery of Potent, Reversible, and Competitive Cruzain Inhibitors with Trypanocidal Activity: A Structure-Based Drug Design Approach
de Souza, M. L., Júnior, C. D. O. R., Ferreira, R. S., Espinoza-Chávez, R. M., Ferreira, L. L. G., Slafer, B. W., Magalhães, L. G., Krogh, R., Oliva, G., Cruz, F. C., et al. (2019) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.9b00802 · Cited by 50
Benzimidazole Inhibitors Induce a DFG-Out Conformation of Never in Mitosis Gene A-Related Kinase 2 (Nek2) without Binding to the Back Pocket and Reveal a Nonlinear Structure−Activity Relationship
Solanki, S., Innocenti, P., Mas-Droux, C., Boxall, K. J., Barillari, C., van Montfort, R. L. M., Aherne, G. W., Bayliss, R. W., & Hoelder, S. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm1011726 · Cited by 50
Optimization of a Fragment-Based Screening Hit toward Potent DOT1L Inhibitors Interacting in an Induced Binding Pocket
Scheufler, C., Möbitz, H., Gaul, C., Ragot, C., Be, C., Fernández, C. F., Beyer, K. S., Tiedt, R., & Stauffer, F. (2016) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6b00168 · Cited by 49
Potent and Selective Inhibitors of CK2 Kinase Identified through Structure-Guided Hybridization
Dowling, J. E., Chuaqui, C. E., Pontz, T. W., Lyne, P. D., Larsen, N., Block, M. H., Chen, H., Su, N., Wu, A. J., Russell, D. J., et al. (2012) · ACS Medicinal Chemistry Letters · doi:10.1021/ml200257n · Cited by 49
SPAM: A Simple Approach for Profiling Bound Water Molecules
Cui, G., Swails, J., & Manas, E. S. (2013) · Journal of Chemical Theory and Computation · doi:10.1021/ct400711g · Cited by 48
Fragment-Based Discovery of Indole Inhibitors of Matrix Metalloproteinase-13
Taylor, S. J., Abeywardane, A., Liang, S., Muegge, I., Padyana, A. K., Xiong, Z., Hill-Drzewi, M., Farmer, B. T., Li, X., Collins, B., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm201129m · Cited by 47
Fragment-based screening by X-ray crystallography, MS and isothermal titration calorimetry to identify PNMT (phenylethanolamine N-methyltransferase) inhibitors
Drinkwater, N., Vu, H., Lovell, K. M., Criscione, K. R., Collins, B. M., Prisinzano, T. E., Poulsen, S., McLeish, M. J., Grunewald, G. L., & Martin, J. L. (2010) · Biochemical Journal · doi:10.1042/bj20100651 · Cited by 45
The Purchasable Chemical Space: A Detailed Picture
Lucas, X., Grüning, B. A., Bleher, S., & Günther, S. (2015) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.5b00116 · Cited by 46
Optimization of Ligand and Lipophilic Efficiency To Identify an in Vivo Active Furano-Pyrimidine Aurora Kinase Inhibitor
Shiao, H., Coumar, M. S., Chun-Wei, C., Ke, Y., Chi, Y., Chu, C., Sun, H.-Y., Chen, C.-H., Lin, W., Fung, K.-S., et al. (2013) · Journal of Medicinal Chemistry · doi:10.1021/jm4006059 · Cited by 44
Molecular Property Filters Describing Pharmacokinetics and Drug Binding
García‐Sosa, A. T., Maran, U., & Hetényi, C. (2012) · Current Medicinal Chemistry · doi:10.2174/092986712799945021 · Cited by 44
Tuning the serum persistence of human serum albumin domain III:diabody fusion proteins
Kenanova, V. E., Olafsen, T., Salazar, F. B., Williams, L. E., Knowles, S. M., & Wu, A. M. (2010) · Protein Engineering Design and Selection · doi:10.1093/protein/gzq054 · Cited by 42
Electron Density Guided Fragment-Based Lead Discovery of Ketohexokinase Inhibitors
Gibbs, A. C., Abad, M. C., Zhang, X., Tounge, B. A., Lewandowski, F. A., Struble, G. T., Sun, W., Sui, Z., & Kuo, L. C. (2010) · Journal of Medicinal Chemistry · doi:10.1021/jm100677s · Cited by 41
Self-citation
In Vivo Evaluation of Selective Carbonic Anhydrase Inhibitors as Potential Anticonvulsant Agents
Bruno, E., Buemi, M. R., Luca, L. D., Ferro, S., Monforte, A., Supuran, C. T., Vullo, D., Sarro, G. D., Russo, E., & Gitto, R. (2016) · ChemMedChem · doi:10.1002/cmdc.201500596 · Cited by 39
Convergent 18 F radiosynthesis: A new dimension for radiolabelling
Li, L., Hopkinson, M. N., Yona, R. L., Béjot, R., Gee, A. D., & Gouverneur, V. (2010) · Chemical Science · doi:10.1039/c0sc00362j · Cited by 38
Discovery of small molecules targeting the tandem tudor domain of the epigenetic factor UHRF1 using fragment-based ligand discovery
Chang, L., Campbell, J. C., Raji, I. O., Guduru, S. K. R., Kandel, P., Nguyen, M., Liu, S., Tran, K., Venugopal, N. K., Taylor, B. C., et al. (2021) · Scientific Reports · doi:10.1038/s41598-020-80588-4 · Cited by 38
Efficiency of hit generation and structural characterization in fragment-based ligand discovery
Larsson, A., Jansson, A. E., Åberg, A., & Nordlund, P. (2011) · Current Opinion in Chemical Biology · doi:10.1016/j.cbpa.2011.06.008 · Cited by 36
Progress in discovery of small-molecule modulators of protein–protein interactions via fragment screening
Magee, T. V. (2015) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2015.04.089 · Cited by 36
Discovery of novel pyrrole-based scaffold as potent and orally bioavailable free fatty acid receptor 1 agonists for the treatment of type 2 diabetes
Li, Z., Pan, M., Su, X., Dai, Y., Fu, M., Cai, X., Shi, W., Huang, W., & Qian, H. (2016) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2016.03.014 · Cited by 34
Proteome‐Wide Fragment‐Based Ligand and Target Discovery
Forrest, I., & Parker, C. G. (2023) · Israel Journal of Chemistry · doi:10.1002/ijch.202200098 · Cited by 31
Pharmacophore modeling and its applications
Tyagi, R., Singh, A., Chaudhary, K. K., & Yadav, M. K. (2021) · Elsevier eBooks · doi:10.1016/b978-0-323-89775-4.00009-2 · Cited by 37
Rational Design Strategies in DNA‐Encoded Libraries for Drug Discovery
Wang, X., Li, L., Shen, X., & Lu, X. (2025) · Angewandte Chemie International Edition · doi:10.1002/anie.202511839 · Cited by 31
Advances in fragment-based drug discovery platforms
Orita, M., Warizaya, M., Amano, Y., Ohno, K., & Niimi, T. (2009) · Expert Opinion on Drug Discovery · doi:10.1517/17460440903317580 · Cited by 32
Aminoindazole PDK1 Inhibitors: A Case Study in Fragment-Based Drug Discovery
Medina, J. R., Blackledge, C. W., Heerding, D. A., Campobasso, N., Ward, P., Briand, J., Wright, L. L., & Axten, J. M. (2010) · ACS Medicinal Chemistry Letters · doi:10.1021/ml100136n · Cited by 30
Binding Evaluation of Fragment-Based Scaffolds for Probing Allosteric Enzymes
Krimm, I., Lancelin, J., & Praly, J. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201439b · Cited by 30
Discovery of biological evaluation of pyrazole/imidazole amides as mGlu5 receptor negative allosteric modulators
Chae, E., Shin, Y., Ryu, E.-J., Ji, M. K., Cho, N. R., Lee, K., Jeong, H. J., Kim, S.-J., Choi, Y., Oh, K. S., et al. (2013) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2013.01.116 · Cited by 28
MDA-9/Syntenin: An emerging global molecular target regulating cancer invasion and metastasis
Das, S. K., Sarkar, D., Emdad, L., & Fisher, P. B. (2019) · Advances in cancer research · doi:10.1016/bs.acr.2019.03.011 · Cited by 28
Fragment-based design, synthesis, and biological evaluation of N-substituted-5-(4-isopropylthiophenol)-2-hydroxynicotinamide derivatives as novel Mcl-1 inhibitors
Zhang, Z., Liu, C., Li, X., Song, T., Wu, Z., Liang, X., Zhao, Y., Shen, X., & Chen, H. (2012) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2012.12.016 · Cited by 27
Grand Canonical Free-Energy Calculations of Protein−Ligand Binding
Clark, M., Meshkat, S., & Wiseman, J. S. (2009) · Journal of Chemical Information and Modeling · doi:10.1021/ci8004397 · Cited by 26
Applications of Solution NMR in Drug Discovery
Li, S., & Zhang, N. (2021) · Molecules · doi:10.3390/molecules26030576 · Cited by 28
β‐Ionone as putative semiochemical suggested by ligand binding on an odorant‐binding protein of Hylamorpha elegans and electroantennographic recordings
Venthur, H., Zhou, J., Mutis, A., Ceballos, R., Mella-Herrera, R. A., Larama, G., Ávila, A. I., Iturriaga‐Vásquez, P., Faundez‐Parraguez, M., Marysol Alvear, Z., et al. (2016) · Entomological Science · doi:10.1111/ens.12180 · Cited by 25
Discovery of novel inhibitors of Aurora kinases with indazole scaffold: In silico fragment-based and knowledge-based drug design
Chang, C.-F., Lin, W., Ke, Y., Lin, Y.-S., Wang, W.-C., Chen, C.-H., Kuo, P., Hsu, J. T. A., Uang, B., & Hsieh, H. (2016) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2016.08.026 · Cited by 25
Computational Study on Potential Novel Anti-Ebola Virus Protein VP35 Natural Compounds
Darko, L. K. S., Broni, E., Amuzu, D. S. Y., Wilson, M. D., Parry, C. S., & Kwofie, S. K. (2021) · Biomedicines · doi:10.3390/biomedicines9121796 · Cited by 25
Deconstruction of Non-Nucleoside Reverse Transcriptase Inhibitors of Human Immunodeficiency Virus Type 1 for Exploration of the Optimization Landscape of Fragments
Brandt, P., Geitmann, M., & Danielson, U. H. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm101052g · Cited by 25
Fragment screening of cyclin G-associated kinase by weak affinity chromatography
Meiby, E., Knapp, S., Elkins, J. M., & Ohlson, S. (2012) · Analytical and Bioanalytical Chemistry · doi:10.1007/s00216-012-6335-6 · Cited by 25
Chemical-Space-Based de Novo Design Method To Generate Drug-Like Molecules
Takeda, S., Kaneko, H., & Funatsu, K. (2016) · Journal of Chemical Information and Modeling · doi:10.1021/acs.jcim.6b00038 · Cited by 25
Computer-aided design, synthesis and biological characterization of novel inhibitors for PKMYT1
Najjar, A., Platzer, C., Luft, A., Aßmann, C., Elghazawy, N. H., Erdmann, F., Sippl, W., & Schmidt, M. (2018) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2018.10.050 · Cited by 25
Do Biologically Relevant Compounds Have More Chance To Be Drugs?
De, K., Ren, W., Lu, W. P., & Zhang, H. (2009) · Journal of Chemical Information and Modeling · doi:10.1021/ci900229c · Cited by 24
De novo fragment-based design of inhibitors of DXS guided by spin-diffusion-based NMR spectroscopy
Masini, T., Pilger, J., Kroezen, B. S., Illarionov, B. A., Lottmann, P., Fischer, M. J., Griesinger, C., & Hirsch, A. K. H. (2014) · Chemical Science · doi:10.1039/c4sc00588k · Cited by 23
Synthesis and Biological Characterization of 3-Substituted-1H-indoles as Ligands of GluN2B-Containing N-Methyl- d -aspartate Receptors
Gitto, R., Luca, L. D., Ferro, S., Buemi, M. R., Russo, E., Sarro, G. D., Costa, L., Ciranna, L., Prezzavento, O., Arena, E., et al. (2011) · Journal of Medicinal Chemistry · doi:10.1021/jm2008002 · Cited by 22
Discovery of Novel Pneumococcal Surface Antigen A (PsaA) Inhibitors Using a Fragment-based Drug Design Approach
Bajaj, M., Mamidyala, S. K., Zuegg, J., Neville, S. L., Ween, M. P., Luo, Z., Huang, J. X., McEwan, A. G., Kobe, B., Paton, J. C., et al. (2015) · ACS Chemical Biology · doi:10.1021/cb501032x · Cited by 21
Allosteric Small-Molecule Serine/Threonine Kinase Inhibitors
Panicker, R. C., Chattopadhaya, S., Coyne, A. G., & Srinivasan, R. (2019) · Advances in experimental medicine and biology · doi:10.1007/978-981-13-8719-7_11 · Cited by 21
From Phenotypic Hit to Chemical Probe: Chemical Biology Approaches to Elucidate Small Molecule Action in Complex Biological Systems
Pasquer, Q. T. L., Tsakoumagkos, I. A., & Hoogendoorn, S. (2020) · Molecules · doi:10.3390/molecules25235702 · Cited by 21
Designing a Diverse High-Quality Library for Crystallography-Based FBDD Screening
Tounge, B. A., & Parker, M. H. (2011) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-381274-2.00001-7 · Cited by 21
Self-citation
Toward a generalized computational workflow for exploiting transient pockets as new targets for small molecule stabilizers: Application to the homogentisate 1,2-dioxygenase mutants at the base of rare disease Alkaptonuria
Bernini, A., Galderisi, S., Spiga, O., Bernardini, G., Niccolai, N., Manetti, F., & Santucci, A. (2017) · Computational Biology and Chemistry · doi:10.1016/j.compbiolchem.2017.08.008 · Cited by 21
Fragment-based screening: A new paradigm for ligand and target discovery
Knight, S., Gianni, D., & Hendricks, A. (2022) · SLAS DISCOVERY · doi:10.1016/j.slasd.2021.10.011 · Cited by 20
Compound Precipitation in High-Concentration DMSO Solutions
Popa-Burke, I. G., & Russell, J. (2014) · SLAS DISCOVERY · doi:10.1177/1087057114541146 · Cited by 19
Identification of potent ITK inhibitors through focused compound library design including structural information
Herdemann, M., Heit, I., Bosch, F.-U., Quintini, G., Scheipers, C., & Weber, A. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.09.119 · Cited by 19
Thermodynamic Proxies to Compensate for Biases in Drug Discovery Methods
Ekins, S., Litterman, N. K., Lipinski, C. A., & Bunin, B. A. (2015) · Pharmaceutical Research · doi:10.1007/s11095-015-1779-y · Cited by 19
Ligand efficiency based approach for efficient virtual screening of compound libraries
Ke, Y., Coumar, M. S., Shiao, H., Wang, W.-C., Chen, C.-W., Song, J., Chen, C.-H., Lin, W., Wu, S.-H., Hsu, J. T.-A., et al. (2014) · European Journal of Medicinal Chemistry · doi:10.1016/j.ejmech.2014.06.029 · Cited by 19
Discovery of a new series of Aurora inhibitors through truncation of GSK1070916
Medina, J. R., Grant, S. W., Axten, J. M., Miller, W. H., Donatelli, C. A., Hardwicke, M. A., Oleykowski, C. A., Liao, Q., Plant, R. N., & Xiang, H. (2010) · Bioorganic & Medicinal Chemistry Letters · doi:10.1016/j.bmcl.2010.02.091 · Cited by 19
Exploring DOXP-reductoisomerase binding limits using phosphonated N-aryl and N-heteroarylcarboxamides as DXR inhibitors
Bodill, T., Conibear, A. C., Mutorwa, M. K., Goble, J. L., Blatch, G. L., Lobb, K. A., Klein, R., & Kaye, P. T. (2013) · Bioorganic & Medicinal Chemistry · doi:10.1016/j.bmc.2013.04.076 · Cited by 18
Fragment-Based Approaches to the Discovery of Kinase Inhibitors
Mortenson, P. N., Berdini, V., & O’Reilly, M. (2014) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/b978-0-12-397918-6.00003-3 · Cited by 18

Authors: Bembenek, S. D., Tounge, B. A., & Reynolds, C. H.
Affiliations: Janssen Research & Development (United States) (US)
Corresponding author: Bembenek, Scott D.
ORCID: Bembenek, Scott D.
Reynolds, Charles H.
Venue: Drug Discovery Today
Publisher: Elsevier BV
Published: 2009-03
Volume: 14
Issue: 5-6
Pages: 278-283
ISSN: 1359-6446 (ISSN-L)
DOI: 10.1016/j.drudis.2008.11.007
OpenAlex: W2086070714
Cited by: 196
References: 23
Citations by year: 2026: 8 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 4 · 2021: 13 · 2020: 2 · 2019: 12 · 2018: 8 · 2017: 10 · 2016: 12 · 2015: 13 · 2014: 15 · 2013: 15 · 2012: 19
FWCI: 21.88
Type: journal article
Language: en
Open access: closed
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/legal/tdmrep-license (tdm)
Locations: Drug Discovery Today (publishedVersion)
PubMed (publishedVersion)
Topics: Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
Keywords: ligand efficiency, fragment-based drug discovery, molecular weight, fragment optimization, hit-to-lead optimization, molecular size dependence
MeSH terms: Humans, Ligands, Molecular Weight, Protein Binding, Drug Delivery Systems, Small Molecule Libraries, Drug Discovery

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Ligand efficiency and fragment-based drug discovery

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Claims other papers make about this one

Citations

Cites

Cited by

Related

Metadata

Record

About these checks