Trend Analysis of a Database of Intravenous Pharmacokinetic Parameters in Humans for 1352 Drug Compounds.The total radioactive Cs concentration in final-instar Stenopsyche marmorata larvae from the Mano River, Fukushima Prefecture, in 2013 was found to be >1000 Bq kg −1 in dry weight. Franco Lombardo, Giuliano Berellini, R.Expert Opinion on Drug Discovery 2019, 14 Strategies to optimize drug half-life in lead candidate identification. Fabio Broccatelli, Cornelis E.C.A Hop, Matthew Wright.Isosteres Modulate Drug Properties without Introducing Inherent Liabilities. Clément Ghiazza, Thierry Billard, Callum Dickson, Anis Tlili, Christian M.Scaffold-hopping as a strategy to address metabolic liabilities of aromatic compounds. Advances in the study of drug metabolism – symposium report of the 12th Meeting of the International Society for the Study of Xenobiotics (ISSX). Scott, Matthew Segall, Ryan Takahashi, Mitchell E. Lauschke, Iain Martin, Chukwunonso Nwabufo, Bhagwat Prasad, Emily E. Russell, Mary Alexandra Schleiff, Eric Gonzalez, Aaron G. Evaluation of Tissue Binding in Three Tissues across Five Species and Prediction of Volume of Distribution from Plasma Protein and Tissue Binding with an Existing Model. Frederick Hsu, Yi-Chen Chen, Fabio Broccatelli.Ligand binding at the protein–lipid interface: strategic considerations for drug design. Molecule Ideation Using Matched Molecular. Sandeep Pal, Peter Pogány, James Andrew Lumley.Indian ayurvedic herb, Boerhaavia diffusa as BCPR inhibitor: The story behind the curtains. Nataša Milošević, Maja Milanović, Nebojša Pavlović, Larisa Đurić, Nunzio Antonio Cacciola, Francesca Borrelli, Nataša Milić.Dual Photoredox/Nickel-Catalyzed Conversion of Aryl Halides to Aryl Aminooxetanes: Computational Evidence for a Substrate-Dependent Switch in Mechanism.
A Retrospective Look at the Impact of Binding Site Environment on the Optimization of TRPA1 Antagonists. Shields, Jun Chen, Steven Magnuson, Matthew Volgraf. Terrett, Robin Larouche-Gauthier, Martin Déry, Huifen Chen, Rebecca M. This article is cited by 13 publications. Decreasing lipophilicity without addressing a metabolic soft-spot will often lead to both lower clearance and lower volume of distribution without extending half-life. This work presents an extensive analysis of Genentech’s in vitro and in vivo rat pharmacokinetic data, which highlights how half-life optimization through simple modulation of lipophilicity is generally not a successful strategy. While both the pharmacokinetic theory and the need for an optimal safety profile support this approach, this needs to be integrated with practical indications concerning the strategy to optimize clearance. The consensus in the field is that decreasing clearance, as opposed to increasing volume of distribution, is a better strategy to prolong half-life. When efficacy is driven by a continuous coverage of the minimum efficacious plasma concentration, half-life must be optimized to achieve the optimal pharmacokinetic profile. The optimization of the pharmacokinetic profile of a drug is one of the crucial aspects of medicinal chemistry campaigns.