The DOI matches its Crossref record; 22 of the 22 references it cites were found in a registry or an index.
Fragment-Based Drug Design: How Big Is Too Big?
Abstract
Much has been discussed about the proper physicochemical properties (e.g., molecular weight, hydrophobicity, etc.) that should be considered when utilizing fragment leads in drug design. However, little has been reported as to what emphasis, if any, should be placed on the potency of the resulting fragment leads. In this report, a retrospective analysis of 18 highly optimized inhibitors is described in which the compounds were systematically deconstructed until the minimal binding elements could be identified. An analysis of the potency changes that were observed as the leads were reduced in size indicate that a nearly linear relationship exists between molecular weight and binding affinity over the entire range of sizes and potencies represented in the dataset. On the basis of these observations, prediction maps can be constructed that enable critical and quantitative assessments of the process of lead identification and optimization. These data place well-defined limits on the ideal size and potency of fragment leads that are being considered for use in fragment-based drug design.
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Cites
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Cited by
Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success
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Perspectives on NMR in drug discovery: a technique comes of age
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Metadata
- Authors
- Hajduk, P. J.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2006-11-09
- Volume
- 49
- Issue
- 24
- Pages
- 6972-6976
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2299973047
- Cited by
- 265
- References
- 22
- FWCI
- 22.89
- Type
- journal article
- Language
- en
- Open access
- closed
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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