Bernard Faller

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This study reports on a novel, high-throughput assay, designed to predict passive, transcellular permeability in early drug discovery. The assay is carried out in 96-well microtiterplates and measures the ability of compounds to diffuse from a donor to an acceptor compartment which are separated by a 9-10 microm hexadecane liquid layer. A set of 32(More)
Alkylamides (alkamides) from Echinacea modulate tumor necrosis factor alpha mRNA expression in human monocytes/macrophages via the cannabinoid type 2 (CB2) receptor (Gertsch, J., Schoop, R., Kuenzle, U., and Suter, A. (2004) FEBS Lett. 577, 563-569). Here we show that the alkylamides dodeca-2E,4E,8Z,10Z-tetraenoic acid isobutylamide (A1) and(More)
The permeability of biological membranes is one of the most important determinants of the pharmacokinetic processes of a drug. Although it is often accepted that many drug substances are transported across biological membranes by passive transcellular diffusion, a recent hypothesis speculated that carrier-mediated mechanisms might account for the majority(More)
This study describes a method for mining and modeling binding data obtained from a large panel of targets (in vitro safety pharmacology) to distinguish differences between promiscuous and selective compounds. Two naïve Bayes models for promiscuity and selectivity were generated and validated on a test set as well as publicly available drug databases. The(More)
Evidence supporting the action of passive diffusion and carrier-mediated (CM) transport in drug bioavailability and disposition is discussed to refute the recently proposed theory that drug transport is CM-only and that new transporters will be discovered that possess transport characteristics ascribed to passive diffusion. Misconceptions and faulty(More)
A microsomal preparation of human prostatic tissue was used to study the kinetics of interaction of steroid 5 alpha-reductase with finasteride, a known 5 alpha-reductase inhibitor. This molecule has been reported to reversibly bind 5 alpha-reductase in a competitive manner to testosterone with a Ki value in the 10 nM range. The results presented in this(More)
Recently, it has been proposed that drug permeation is essentially carrier-mediated only and that passive lipoidal diffusion is negligible. This opposes the prevailing hypothesis of drug permeation through biological membranes, which integrates the contribution of multiple permeation mechanisms, including both carrier-mediated and passive lipoidal(More)
The aim of this study was to understand which parameters are responsible for the selective modulation of compounds solubility in simulated intestinal fluids. The solubility of 25 chemically diverse reference compounds was measured in simulated intestinal fluid (FaSSIF-V2) and in aqueous phosphate and maleate buffers. Electrostatic interactions between(More)
Although reversible CYP3A inhibition testing is well established for predicting the drug-drug interaction potential of clinical candidates, time-dependent inhibition (TDI) has become the focus of drug designers only recently. Failure of several late-stage clinical candidates has been attributed to TDI, and this mechanism is also suspected to play a role in(More)