Physiochemical drug properties associated with in vivo toxicological outcomes.

By J. Hughes, J. Blagg, David A. Price, S. Bailey, G. Decrescenzo, R. Devraj, E. Ellsworth, Y. M. Fobian, M. Gibbs, Richard Gilles and 7 more. Bioorganic & Medicinal Chemistry Letters, 2008

901 citations recorded by the source corpus.

Subfields: Computational Theory and Mathematics, Pharmacology, Spectroscopy

View Paper: https://www.semanticscholar.org/paper/bdb240ecf02ed81ce455ccc02ff081571ae065fb

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Citations in the corpus

EASL Clinical Practice Guidelines: Drug-induced liver injury. (2019, background): “Drugs with higher lipophilicity appear to have increased off-target binding as well as an increased likelihood of causing toxic events in general.(122) Lipophilicity combined with daily dose, referred to as the ‘‘rule-of-two”, has been suggested to reflect a drug’s hepatotoxic potential, with high l”
The rise of fragment-based drug discovery. (2009, background): “Moreover, an increased likelihood of toxic events has been reported for less polar, more lipophilic compounds, indicating the importance of the total polar surface area as well as lipophilicity on attritio”
Automated design of ligands to polypharmacological profiles (2012, background): “Comparison of the predicted Bayesian and observed polypharmacology profiles for (1) donepezil (compound 1); (2) the isoindole analogues (compounds 2–8)—of the 160 ligand– target associations, 100 were correctly predicted by the Bayesian models (P 5 0.”
Moving beyond rules: the development of a central nervous system multiparameter optimization (CNS MPO) approach to enable alignment of druglike properties. (2010, background): “0 or design was confined to low-risk space as defined by the 3 and 75 relative risk factors (13), the PDE-10 inhibitor and the H3 antagonist, respectively, would have not been synthesized.”
The influence of lipophilicity in drug discovery and design (2012, background): “However, compounds that achieve their potency through lipophilic interactions are likely to be less selective and more promiscuous, running the risk of off-target interactions and unwanted toxicity [8,13].”
Virtual screening strategies in drug discovery: a critical review. (2013, background): “Recently, Pfizer's "Rule of 3/75" has been described which states that compounds with a calculated partition coefficient (ClogP) of < 3 and topological polar surface area (TPSA) > 75 have the best chances of being well tolerated from a safety perspective in vivo [15].”
The impact of aromatic ring count on compound developability--are too many aromatic rings a liability in drug design? (2009, background): “More recent literature correlates increased molecular lipophilicity with the risk of adverse toxicological events [2, 10 ] .A lthough the drugability of current targets is often lower than that of historical targets, and there are examples of highly lipophilic drugs on the market, this analysis sugg”