The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Two Decades under the Influence of the Rule of Five and the Changing Properties of Approved Oral Drugs: Miniperspective
Abstract
Two decades have passed since the rule of five ushered in the concept of "drug-like" properties. Attempts to quantify, correlate, and categorize molecules based on Ro5 parameters evolved into the introduction of efficiency metrics with far reaching consequences in decision making by industry leaders and scientists seeking to discover new medicines. Examination of oral drug parameters approved before and after the original Ro5 analysis demonstrates that some parameters such as clogP and HBD remained constant while the cutoffs for parameters such as molecular weight and HBA have increased substantially over the past 20 years. The time dependent increase in the molecular weight of oral drugs during the past 20 years provides compelling evidence to disprove the hypothesis that molecular weight is a "drug-like" property. This analysis does not validate parameters that have not changed as being "drug-like" but instead calls into question the entire hypothesis that "drug-like" properties exist.
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Lipinski, C. A., Lombardo, F., Dominy, B. W., & Feeney, P. J. (1997) · Advanced Drug Delivery Reviews · doi:10.1016/s0169-409x(96)00423-1 · Cited by 11,385
Molecular properties that influence the oral bioavailability of drug candidates
Veber, D. F., Johnson, S. R., Cheng, H.-Y., Smith, B. R., Ward, K. W., & Kopple, K. D. (2002) · Journal of Medicinal Chemistry · doi:10.1021/jm020017n · Cited by 8,420
Escape from Flatland: Increasing Saturation as an Approach to Improving Clinical Success
Lovering, F., Bikker, J., & Humblet, C. (2009) · Journal of Medicinal Chemistry · doi:10.1021/jm901241e · Cited by 4,495
Can the pharmaceutical industry reduce attrition rates?
Kola, I., & Landis, J. (2004) · Nature Reviews Drug Discovery · doi:10.1038/nrd1470 · Cited by 4,167
How to improve R&D productivity: the pharmaceutical industry's grand challenge
Paul, S. M., Mytelka, D. S., Dunwiddie, C. T., Persinger, C. C., Munos, B. H., Lindborg, S. R., & Schacht, A. L. (2010) · Nature Reviews Drug Discovery · doi:10.1038/nrd3078 · Cited by 3,566
Quantifying the chemical beauty of drugs
Bickerton, G. R., Paolini, G. V., Besnard, J., Muresan, S., & Hopkins, A. L. (2012) · Nature Chemistry · doi:10.1038/nchem.1243 · Cited by 2,242
Diagnosing the decline in pharmaceutical R&D efficiency
Scannell, J. W., Blanckley, A., Boldon, H., & Warrington, B. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3681 · Cited by 1,981
Ertl, P., & Schuffenhauer, A. (2009) · Journal of Cheminformatics · doi:10.1186/1758-2946-1-8 · Cited by 1,939
Ligand efficiency: a useful metric for lead selection
Hopkins, A. L., Groom, C. R., & Alex, A. (2004) · Drug Discovery Today · doi:10.1016/s1359-6446(04)03069-7 · Cited by 1,846
Enumeration of 166 Billion Organic Small Molecules in the Chemical Universe Database GDB-17
Ruddigkeit, L., van Deursen, R., Blum, L. C., & Reymond, J.-L. (2012) · Journal of Chemical Information and Modeling · doi:10.1021/ci300415d · Cited by 1,505
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BackgroundMolecular Sets (MOSES): A Benchmarking Platform for Molecular Generation Models
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Metadata
- Authors
- Shultz, M. D.
- Venue
- Journal of Medicinal Chemistry
- Publisher
- American Chemical Society (ACS)
- Published
- 2018-09-13
- Volume
- 62
- Issue
- 4
- Pages
- 1701-1714
- ISSN
- 0022-2623 (ISSN-L)
- 1520-4804
- OpenAlex
- W2891800472
- Cited by
- 434
- References
- 68
- FWCI
- 28.05
- Type
- journal article
- Language
- en
- Open access
- closed
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- Shultz, M. D. (2019). Two Decades under the Influence of the Rule of Five and the Changing Properties of Approved Oral Drugs: Miniperspective. Journal of Medicinal Chemistry. https://doi.org/10.1021/acs.jmedchem.8b00686
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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