The DOI matches its Crossref record; 23 of the 23 references it cites were found in a registry or an index.
Ligand efficiency and fragment-based drug discovery
Abstract
The use of fragment-based drug discovery (FBDD) has increased in recent years since it is more likely to produce a better optimized compound of lower molecular weight. Ligand efficiency (LE) has become important for assessing fragments, HTS hits, and resulting optimized ligands. LE is useful for comparing ligands of equal molecular weight, but is ineffective for comparisons of ligands of differing molecular weight. LE has a strong dependence on molecular size, which has led us to develop a size-independent efficiency score termed fit quality. Evaluating FBDD examples from the literature using LE and fit quality, we find that, in general, the LEs of starting fragments are greater than those of larger, more elaborated, structures. Fit quality scores, however, tend to improve upon optimization of the fragments.
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“Fragment-based ligand discovery (FBLD) has emerged as a versatile approach for the discovery of atom-efficient, small-molecule binders for a wide range of proteins10–12.”
From Expedited mapping of the ligandable proteome using fully functionalized enantiomeric probe pairs (2019) · cites this paper as [10]
Citations
Cites
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Molecular Complexity and Its Impact on the Probability of Finding Leads for Drug Discovery
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Items 201–223 of 223
BindingDB (2011) · UC San Diego · doi:10.7270/q2z038d4
BindingDB (2014) · UC San Diego · doi:10.7270/q2dv1mb8
BindingDB (2010) · UC San Diego · doi:10.7270/q2348kdc
BindingDB (2013) · UC San Diego · doi:10.7270/q21j9bs9
BindingDB (2011) · UC San Diego · doi:10.7270/q22807wj
BindingDB (2012) · UC San Diego · doi:10.7270/q2c53m9c
BindingDB (2010) · UC San Diego · doi:10.7270/q2ws8tdz
BindingDB (2017) · UC San Diego · doi:10.7270/q2p84drx
BindingDB (2020) · UC San Diego · doi:10.7270/q2251mpr
BindingDB (2020) · UC San Diego · doi:10.7270/q2cc13cc
Metadata
- Authors
- Bembenek, S. D., Tounge, B. A., & Reynolds, C. H.
- Affiliations
- Janssen Research & Development (United States) (US)
- Corresponding author
- Bembenek, Scott D.
- Venue
- Drug Discovery Today
- Publisher
- Elsevier BV
- Published
- 2009-03
- Volume
- 14
- Issue
- 5-6
- Pages
- 278-283
- ISSN
- 1359-6446 (ISSN-L)
- OpenAlex
- W2086070714
- Cited by
- 196
- References
- 23
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 8 · 2023: 6 · 2022: 4 · 2021: 13 · 2020: 2 · 2019: 12 · 2018: 8 · 2017: 10 · 2016: 12 · 2015: 13 · 2014: 15 · 2013: 15 · 2012: 19
- FWCI
- 21.88
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Drug Discovery Today (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Drug Discovery › Computational Drug Discovery Methods
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Synthesis and Analysis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
- Keywords
- ligand efficiency, fragment-based drug discovery, molecular weight, fragment optimization, hit-to-lead optimization, molecular size dependence
- MeSH terms
- Humans, Ligands, Molecular Weight, Protein Binding, Drug Delivery Systems, Small Molecule Libraries, Drug Discovery
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