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Expert Opinion on Drug Metabolism & Toxicology Volume 2, 2006 - Issue 2
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Technology Evaluation

Focus on success: using a probabilistic approach to achieve an optimal balance of compound properties in drug discovery

Matt D Segall Head of Admensa Business Unit, Inpharmatica Ltd, 127 Cambridge Science Park, Milton Road, Cambridge, UK
,
Alan P Beresford Director, Lead Optimisation, Inpharmatica Ltd, 127 Cambridge Science Park, Milton Road, Cambridge, UK
,
Joelle MR Gola Computational Chemist, Inpharmatica Ltd, 127 Cambridge Science Park, Milton Road, Cambridge, UK
,
Dan Hawksley Senior Scientist, Lead Optimisation, Inpharmatica Ltd, 127 Cambridge Science Park, Milton Road, Cambridge, UK
&
Mike H Tarbit SVP preclinical R&D, Inpharmatica Ltd, 127 Cambridge Science Park, Milton Road, Cambridge, UK
Pages 325-337 | Published online: 24 Mar 2006

Bibliography

  • BAXTER A, BROUGH S, COOPER A etal.: Hit-to-lead studies: the discovery of potent, orally active, thiophenecarboxamide IKK-2 inhibitors. Bioorg. Med. Chem. Lett. (2004) 14:2817-2822.
  • BAXTER A, BENT J, BOWERS K etal.: Hit-to-lead studies: the discovery of potent adamantane amide P2X7 receptor antagonists. Bioorg. Med. Chem. Lett. (2003) 13:4047-4050.
  • MATHEW N T, LODER EW: Evaluating the triptans. Am. J. Med. (2005) 118(Suppl.1):28S-35S.
  • RICHARDSON K, COOPER K, MARRIOTT MS, TARBIT MH, TROKEPF, WHITTLE PJ: Discovery of fluconazole, a novel antifungal agent. Rev. Infect. Dis. (1990) 12(Suppl. 3):S267-S271.
  • STOPHER D A, BERESFORD AP, MACRAE PV, HUMPHREY MJ: The metabolism and pharmacokinetics of amlodipine in humans and animals. J. Cardiovasc. Pharmacol. (1988) 12(Suppl.7):S55-S59.
  • DAVIS AM, RILEY RJ: Predictive ADMET studies, the challenges and the opportunities. Curr. Opin. Chem. Biol. (2004) 8:378-386.
  • STOUCH T R, KENYON JR, JOHNSON SR, CHEN XQ, DOWEYKOA, LI Y: In silico ADME/Tox: why models fail. J. Comput. Aided Mol. Des. (2003) 17:83-92.
  • OPREA TI: Virtual screening in lead discovery: a viewpoint. Molecules (2002) 7:51-62.
  • SHIMANDA J, EKINS S, ELKIN C, SHAKHNOVICH EI, WERY J-P: Integrating computer-based denovo drug design and multidimensional filtering for desirable drugs. Targets (2002) 1:196-205.
  • BERESFORD A P, SEGALL M, TARBITMH: In silico prediction of ADME properties: are we making progress? Curr. Opin Drug Discov. Devel. (2004) 7:36-42.
  • VAN DE WATERBEEMD H, GIFFORDE: ADMET in silico modelling: towards prediction paradise? Nat. Rev. Drug Discov. (2003) 2:192-204.
  • EKINS S, BOULANGER B, SWAAN PW, HUPCEY MA: Towards a new age of virtual ADME/TOX and multidimensional drug discovery. J. Comput. Aided Mol. Des. (2002) 16:381-401.
  • BERESFORD A P, SEGALL M, TARBITMH: What lies in the future for in silico ADME? Can we predict its evolution? Screening (2004) 3:22-24.
  • NOLLER J, SCHMITT J, HARTMANNT, LOFFLER T: Just married invitro assays and in silico ADME prediction. Screening (2005) 1:32-33.
  • DEWITTE RS: On experimental design in drug discovery. Curr. Drug Disc. (2002) 2:19-22.
  • WOLD S, SJOSTROM M, ERIKSSON L: Partial least squares projections to latent structures (PLS) in chemistry. In: Chemistry Encyclopedia of Computational Chemistry. Elsevier, Amsterdam, The Netherlands (1999):1-16.
  • QUINLAN R: Induction of decision trees. Machine Learning (1986) 1:81-106.
  • MARTIN D, BUHMANN: Radial basis functions: theory and implementations. Cambridge University Press, Cambridge, UK (2003).
  • AGRAFIOTIS DK: Multiobjective optimization of combinatorial libraries. IBM J. Res. & Dev. (2001) 45:545-566.
  • BERESFORD AP, MCGIBNEY D, HUMPHREY MJ, MACRAE PV, STOPHER DA: Metabolism and kinetics of amlodipine in man. Xenobiotica (1988) 18:245-254.
  • KENNEDY T: Managing the drug discovery/development interface. Drug Discov. Today (1997) 2:436-444.
  • KUBINYI H: Drug research: myths, hype and reality. Nat. Rev. Drug Discov. (2003) 2:665-668.
  • TARBIT MH, BERMAN J: High-throughput approaches for evaluating absorption, distribution, metabolism and excretion properties of lead compounds. Curr. Opin. Chem. Biol. (1998) 2:411-416.
  • LIPINSKI C A, LOMBARDO F, DOMINY BW, FEENEY PJ: Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings. Adv. Drug Deliv. Rev. (1997) 23:3-25.
  • WILLMANN S, LIPPERT J, SCHMITTW: From physicochemistry to absorption and distribution: predictive mechanistic modelling and computational tools. Expert Opin. Drug Metab. Toxicol. (2005) 1:159-168.
  • STONER CL, GIFFORD E, STANKOVIC C etal.: Implementation of an ADME enabling selection and visualization tool for drug discovery. J. Pharm. Sci. (2004) 93:1131-1141.

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