Drug research: myths, hype and reality

Kubinyi, Hugo

doi:10.1038/nrd1156

Cited by 340 publications

(207 citation statements)

References 24 publications

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“…63 Improving the affi nity of a chemical lead against a defi ned protein target can be readily quantifi ed, but determining the relative selectivity against all potential targets is impractical. The main challenge is in identifying proteins that may be inadvertent targets of the chemical lead.…”

Section: Application Of Cpass In Drug Discoverymentioning

confidence: 99%

Comparison of protein active site structures for functional annotation of proteins and drug design

et al. 2006

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Rapid and accurate functional assignment of novel proteins is increasing in importance, given the completion of numerous genome sequencing projects and the vastly expanding list of unannotated proteins. Traditionally, global primary‐sequence and structure comparisons have been used to determine putative function. These approaches, however, do not emphasize similarities in active site configurations that are fundamental to a protein's activity and highly conserved relative to the global and more variable structural features. The Comparison of Protein Active Site Structures (CPASS) database and software enable the comparison of experimentally identified ligand‐binding sites to infer biological function and aid in drug discovery. The CPASS database comprises the ligand‐defined active sites identified in the protein data bank, where the CPASS program compares these ligand‐defined active sites to determine sequence and structural similarity without maintaining sequence connectivity. CPASS will compare any set of ligand‐defined protein active sites, irrespective of the identity of the bound ligand. Proteins 2006. © 2006 Wiley‐Liss, Inc.

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Section: Application Of Cpass In Drug Discoverymentioning

confidence: 99%

Comparison of protein active site structures for functional annotation of proteins and drug design

et al. 2006

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“…Apart from efficacy and toxicity, many failures during drug development are related to pharmacokinetics, i.e., the fate of the compound in the organism 1. Nowadays, by monitoring physicochemical profiles of lead compounds it is possible to increase the quality of clinical candidates 2.…”

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confidence: 99%

A BOILED‐Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules

2016

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Apart from efficacy and toxicity, many drug development failures are imputable to poor pharmacokinetics and bioavailability. Gastrointestinal absorption and brain access are two pharmacokinetic behaviors crucial to estimate at various stages of the drug discovery processes. To this end, the Brain Or IntestinaL EstimateD permeation method (BOILED‐Egg) is proposed as an accurate predictive model that works by computing the lipophilicity and polarity of small molecules. Concomitant predictions for both brain and intestinal permeation are obtained from the same two physicochemical descriptors and straightforwardly translated into molecular design, owing to the speed, accuracy, conceptual simplicity and clear graphical output of the model. The BOILED‐Egg can be applied in a variety of settings, from the filtering of chemical libraries at the early steps of drug discovery, to the evaluation of drug candidates for development.

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“…Drug toxicity is a common cause of clinical failures [51], where this toxicity is associated with non-specific in vivo protein activity [52]. In practice, it is not possible to screen against every potential protein target that may bind a chemical lead.…”

Section: Cpassmentioning

confidence: 99%

The application of FAST-NMR for the identification of novel drug discovery targets

Powers

Mercier

Copeland

2008

Drug Discovery Today

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Drug research: myths, hype and reality

Cited by 340 publications

References 24 publications

Comparison of protein active site structures for functional annotation of proteins and drug design

Comparison of protein active site structures for functional annotation of proteins and drug design

A BOILED‐Egg To Predict Gastrointestinal Absorption and Brain Penetration of Small Molecules

The application of FAST-NMR for the identification of novel drug discovery targets

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