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Perspective

Drug efficiency: a new concept to guide lead optimization programs towards the selection of better clinical candidates

(Director) , (Senior Scientific Investigator) , (VP) & (SVP, Head of Neurosciences Centre of Excellence for Drug Discovery)
Pages 609-618 | Published online: 20 May 2010

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Maria Maddalena Cavalluzzi, Giuseppe Felice Mangiatordi, Orazio Nicolotti & Giovanni Lentini. (2017) Ligand efficiency metrics in drug discovery: the pros and cons from a practical perspective. Expert Opinion on Drug Discovery 12:11, pages 1087-1104.
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Deepak Dalvie, Amit S. Kalgutkar & Weichao Chen. (2015) Practical approaches to resolving reactive metabolite liabilities in early discovery. Drug Metabolism Reviews 47:1, pages 56-70.
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Ziqiang Cheng, Houfu Liu, Na Yu, Fei Wang, Gang An, Yan Xu, Qian Liu, Chen-bing Guan & Andrew Ayrton. (2012) Hydrophilic anti-migraine triptans are substrates for OATP1A2, a transporter expressed at human blood-brain barrier. Xenobiotica 42:9, pages 880-890.
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Dino Montanari, Elisabetta Chiarparin, Matthew Paul Gleeson, Simone Braggio, Raffaele Longhi, Klara Valko & Tino Rossi. (2011) Application of drug efficiency index in drug discovery: a strategy towards low therapeutic dose. Expert Opinion on Drug Discovery 6:9, pages 913-920.
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Mario Pellegatti, Sabrina Pagliarusco, Lara Solazzo & Dimitri Colato. (2011) Plasma protein binding and blood-free concentrations: which studies are needed to develop a drug?. Expert Opinion on Drug Metabolism & Toxicology 7:8, pages 1009-1020.
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Mario Pellegatti & Sabrina Pagliarusco. (2011) Drug and metabolite concentrations in tissues in relationship to tissue adverse findings: a review. Expert Opinion on Drug Metabolism & Toxicology 7:2, pages 137-146.
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Laura Zonzini, Federica Bianchi, Nicola Cesari & Matteo Sartori. (2010) In vivo rat PK profiling in drug discovery: new challenges. Expert Opinion on Drug Discovery 5:11, pages 1031-1037.
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Randy R. Miller, Maria Madeira, Harold B. Wood, Wayne M. Geissler, Conrad E. Raab & Iain J. Martin. (2020) Integrating the Impact of Lipophilicity on Potency and Pharmacokinetic Parameters Enables the Use of Diverse Chemical Space during Small Molecule Drug Optimization. Journal of Medicinal Chemistry 63:21, pages 12156-12170.
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Klára L. Valkó. 2020. Separation Methods in Drug Synthesis and Purification. Separation Methods in Drug Synthesis and Purification 667 758 .
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Shenaz B. Bunally, Christopher N. Luscombe & Robert J. Young. (2019) Using Physicochemical Measurements to Influence Better Compound Design. SLAS Discovery 24:8, pages 791-801.
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Vaibhav A. Dixit. (2019) A simple model to solve a complex drug toxicity problem. Toxicology Research 8:2, pages 157-171.
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Serge Mignani, João Rodrigues, Helena Tomas, Rachid Jalal, Parvinder Pal Singh, Jean-Pierre Majoral & Ram A. Vishwakarma. (2018) Present drug-likeness filters in medicinal chemistry during the hit and lead optimization process: how far can they be simplified?. Drug Discovery Today 23:3, pages 605-615.
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Simon Teague & Klara Valko. (2017) How to identify and eliminate compounds with a risk of high clinical dose during the early phase of lead optimisation in drug discovery. European Journal of Pharmaceutical Sciences 110, pages 37-50.
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Fabrizio Micheli. (2017) Novel, Selective, and Developable Dopamine D 3 Antagonists with a Modified “Amino” Region . ChemMedChem 12:16, pages 1254-1260.
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M.P. Gleeson & D. Montanari. 2017. Comprehensive Medicinal Chemistry III. Comprehensive Medicinal Chemistry III 64 93 .
M.M. Hann, M.K. Bayliss & A.R. Leach. 2017. Comprehensive Medicinal Chemistry III. Comprehensive Medicinal Chemistry III 560 576 .
Klára L. Valkó. (2016) Lipophilicity and biomimetic properties measured by HPLC to support drug discovery. Journal of Pharmaceutical and Biomedical Analysis 130, pages 35-54.
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Serge Mignani, Scot Huber, Helena Tomás, João Rodrigues & Jean-Pierre Majoral. (2016) Compound high-quality criteria: a new vision to guide the development of drugs, current situation. Drug Discovery Today 21:4, pages 573-584.
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J. Willem M. Nissink, Sebastien Degorce & Ken Page. 2016. Lead Generation. Lead Generation 451 486 .
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Ken M. Page. (2016) Validation of Early Human Dose Prediction: A Key Metric for Compound Progression in Drug Discovery. Molecular Pharmaceutics 13:2, pages 609-620.
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Fabrizio Micheli, Susanna Cremonesi, Teresa Semeraro, Luca Tarsi, Silvia Tomelleri, Paolo Cavanni, Beatrice Oliosi, Elisabetta Perdonà, Anna Sava, Laura Zonzini, Aldo Feriani, Simone Braggio & Christian Heidbreder. (2016) Novel morpholine scaffolds as selective dopamine (DA) D3 receptor antagonists. Bioorganic & Medicinal Chemistry Letters 26:4, pages 1329-1332.
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Patrick Barton & Robert J. Riley. (2016) A new paradigm for navigating compound property related drug attrition. Drug Discovery Today 21:1, pages 72-81.
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Alexander G. Shard, Rasmus Havelund, Steve J. Spencer, Ian S. Gilmore, Morgan R. Alexander, Tina B. Angerer, Satoka Aoyagi, Jean-Paul Barnes, Anass Benayad, Andrzej Bernasik, Giacomo Ceccone, Jonathan D. P. Counsell, Christopher Deeks, John S. Fletcher, Daniel J. Graham, Christian Heuser, Tae Geol Lee, Camille Marie, Mateusz M. Marzec, Gautam Mishra, Derk Rading, Olivier Renault, David J. Scurr, Hyun Kyong Shon, Valentina Spampinato, Hua Tian, Fuyi Wang, Nicholas Winograd, Kui Wu, Andreas Wucher, Yufan Zhou & Zihua Zhu. (2015) Measuring Compositions in Organic Depth Profiling: Results from a VAMAS Interlaboratory Study. The Journal of Physical Chemistry B 119:33, pages 10784-10797.
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Elizabeth Kwong. (2015) Advancing Drug Discovery: A Pharmaceutics Perspective. Journal of Pharmaceutical Sciences 104:3, pages 865-871.
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Michael M. Hann. 2015. Multifaceted Roles of Crystallography in Modern Drug Discovery. Multifaceted Roles of Crystallography in Modern Drug Discovery 183 196 .
Robert J. Young. 2015. Tactics in Contemporary Drug Design. Tactics in Contemporary Drug Design 1 68 .
Serge Mignani, Saïd El Kazzouli, Mosto Bousmina & Jean-Pierre Majoral. (2013) Dendrimer space concept for innovative nanomedicine: A futuristic vision for medicinal chemistry. Progress in Polymer Science 38:7, pages 993-1008.
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Celerino Abad-Zapatero. 2013. Ligand Efficiency Indices for Drug Discovery. Ligand Efficiency Indices for Drug Discovery 49 62 .
Klara Valko, Elisabetta Chiarparin, Shenaz Nunhuck & Dino Montanari. (2012) In Vitro Measurement of Drug Efficiency Index to Aid Early Lead Optimization. Journal of Pharmaceutical Sciences 101:11, pages 4155-4169.
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Michael M. Hann & György M. Keserü. (2012) Finding the sweet spot: the role of nature and nurture in medicinal chemistry. Nature Reviews Drug Discovery 11:5, pages 355-365.
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Alleyn T. Plowright, Craig Johnstone, Jan Kihlberg, Jonas Pettersson, Graeme Robb & Richard A. Thompson. (2012) Hypothesis driven drug design: improving quality and effectiveness of the design-make-test-analyse cycle. Drug Discovery Today 17:1-2, pages 56-62.
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Tino Rossi & Simone Braggio. (2011) Quality by Design in lead optimization: a new strategy to address productivity in drug discovery. Current Opinion in Pharmacology 11:5, pages 515-520.
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Robert J. Young, Darren V.S. Green, Christopher N. Luscombe & Alan P. Hill. (2011) Getting physical in drug discovery II: the impact of chromatographic hydrophobicity measurements and aromaticity. Drug Discovery Today 16:17-18, pages 822-830.
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