ArticleJournal of medicinal chemistry2019
Why Some Targets Benefit from beyond Rule of Five Drugs.
Article in Journal of medicinal chemistry, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed.
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- Toward Reconciling the Standard Binding Free Energy of Lenacapavir to HIV-1 Capsid with Experiment: Thermodynamic Effects of Solvent Buffer and Ligand Reorganization.The journal of physical chemistry. B · 2026Article
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- E-FTMap: A Protein Structure Based Pharmacophore Identification Server for Guiding Fragment Expansion.Journal of molecular biology · 2025Article
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- Potent phytoregulators from3 Biotech · 2025Article
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- Review
- Non-spike protein inhibition of SARS-CoV-2 by natural products through the key mediator protein ORF8.Molecular biology research communications · 2025Article
- Exploring the Potential of Adaptive, Local Machine Learning in Comparison to the Prediction Performance of Global Models: A Case Study from Bayer's Caco-2 Permeability Database.Journal of chemical information and modeling · 2024Article
- Identification of readily available pseudo-natural products.RSC medicinal chemistry · 2024Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors.
Funding
Abstract
Beyond rule-of-five (bRo5) compounds are increasingly used in drug discovery. Here we analyze 37 target proteins that have bRo5 drugs or clinical candidates. Targets can benefit from bRo5 drugs if they have "complex" hot spot structure with four or more hots spots, including some strong ones. Complex I targets show positive correlation between binding affinity and molecular weight. These targets are conventionally druggable, but reaching additional hot spots enables improved pharmaceutical properties. Complex II targets, mostly protein kinases, also have strong hot spots but show no correlation between affinity and ligand molecular weight, and the primary motivation for creating larger drugs is to increase selectivity. Each target considered as complex III has some specific reason for requiring bRo5 drugs. Finally, targets with "simple" hot spot structure, i.e., three or fewer weak hot spots, must use larger compounds that interact with surfaces beyond the hot spot region to achieve acceptable affinity.
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What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.