• Publications
  • Influence
The influence of lead discovery strategies on the properties of drug candidates
Despite the widespread acceptance of guidelines related to desirable physicochemical properties of potential small-molecule drugs, key properties — such as lipophilicity — of recently developedExpand
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Hit discovery and hit-to-lead approaches.
Hit discovery technologies range from traditional high-throughput screening to affinity selection of large libraries, fragment-based techniques and computer-aided de novo design, many of which haveExpand
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Measuring molecular similarity and diversity: total pharmacophore diversity.
  • G. Makara
  • Chemistry, Medicine
  • Journal of medicinal chemistry
  • 25 October 2001
A novel method, total pharmacophore diversity (ToPD), based on known pharmacophore features for numerically defining molecular similarity or diversity is described. The method captures the 3D shapeExpand
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Rhodopsin-transducin interface: studies with conformationally constrained peptides.
To probe the interaction between transducin (G(t)) and photoactivated rhodopsin (R*), 14 analog peptides were designed and synthesized restricting the backbone of the R*-bound structure of theExpand
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Identification of a small molecule nonpeptide active site beta-secretase inhibitor that displays a nontraditional binding mode for aspartyl proteases.
A small molecule nonpeptide inhibitor of beta-secretase has been developed, and its binding has been defined through crystallographic determination of the enzyme-inhibitor complex. The molecule isExpand
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Hit-to-Lead Optimization and Discovery of 5-((5-([1,1'-Biphenyl]-4-yl)-6-chloro-1H-benzo[d]imidazol-2-yl)oxy)-2-methylbenzoic Acid (MK-3903): A Novel Class of Benzimidazole-Based Activators of
AMP-activated protein kinase (AMPK) plays an essential role as a cellular energy sensor and master regulator of metabolism in eukaryotes. Dysregulated lipid and carbohydrate metabolism resulting fromExpand
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Synthesis and modeling studies with monocyclic analogues of mycophenolic acid.
Two stepwise procedures, developed for the introduction of the (E)-4-methyl-4-hexenoic acid side chain of mycophenolic acid, were used in the synthesis of monocyclic mycophenolic acid analogues 2a-i.Expand
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On sampling of fragment space.
  • G. Makara
  • Medicine, Chemistry
  • Journal of medicinal chemistry
  • 14 June 2007
Fragment-based lead discovery has over the years matured into an attractive alternative to high-throughput screening (HTS) for lead generation. Several techniques for screening libraries of typicallyExpand
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Label-free high-throughput screening via mass spectrometry: a single cystathionine quantitative method for multiple applications.
Label-free mass spectrometric (MS) technologies are particularly useful for enzyme assay design for drug discovery screens. MS permits the selective detection of enzyme substrates or products in aExpand
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On the conformation of tiazofurin analogues.
Tiazofurin, an important inhibitor of inosine 5'-monophosphate dehydrogenase, has been argued to possess a restricted glycosylic bond due to an energetically favorable intramolecular (1-4)Expand
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