Progress in predicting human ADME parameters in silico

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings 1PII of original article: S0169-409X(96)00423-1. The article was originally published in Advanced Drug Delivery Reviews 23 (1997) 3–25. 1

2001 • 16,438 citations

Experimental and computational approaches to estimate solubility and permeability in drug discovery and development settings

1997 • 9,861 citations

Partial least-squares regression: a tutorial

1986 • 6,591 citations

Comparative molecular field analysis (CoMFA). 1. Effect of shape on binding of steroids to carrier proteins

1988 • 3,852 citations

A computational procedure for determining energetically favorable binding sites on biologically important macromolecules

1985 • 2,597 citations

Physicochemical High Throughput Screening: Parallel Artificial Membrane Permeation Assay in the Description of Passive Absorption Processes

1998 • 1,205 citations

Prediction of human clearance of twenty-nine drugs from hepatic microsomal intrinsic clearance data: An examination of in vitro half-life approach and nonspecific binding to microsomes.

1999 • 1,154 citations

Effect of Partial Ileal Bypass Surgery on Mortality and Morbidity from Coronary Heart Disease in Patients with Hypercholesterolemia

1990 • 999 citations

MDCK (Madin-Darby Canine Kidney) Cells: A Tool for Membrane Permeability Screening

1999 • 895 citations

E-CELL: software environment for whole-cell simulation.

1999 • 781 citations

Polar molecular surface as a dominating determinant for oral absorption and brain penetration of drugs.

1999 • 757 citations

Use of In Vitro and In Vivo Data to Estimate the Likelihood of Metabolic Pharmacokinetic Interactions

1997 • 755 citations

Polar molecular surface properties predict the intestinal absorption of drugs in humans.

1997 • 721 citations

Pharmacophore perception, development, and use in drug design

2000 • 683 citations

Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 1. Prediction of intestinal absorption

1999 • 569 citations

Molecular fields in quantitative structure–permeation relationships: the VolSurf approach

2000 • 550 citations

Computational methods for the prediction of ‘drug-likeness’

2000 • 543 citations

Rapid calculation of polar molecular surface area and its application to the prediction of transport phenomena. 2. Prediction of blood–brain barrier penetration

1999 • 499 citations

Modulators and substrates of P-glycoprotein and cytochrome P4503A coordinately up-regulate these proteins in human colon carcinoma cells.

1996 • 487 citations

Prediction of in vivo drug metabolism in the human liver from in vitro metabolism data

1997 • 460 citations

Positively Cooperative Sites for Drug Transport by P‐Glycoprotein with Distinct Drug Specificities

1997 • 450 citations

Correlating partitioning and caco-2 cell permeability of structurally diverse small molecular weight compounds.

1998 • 429 citations

Predicting Blood−Brain Barrier Permeation from Three-Dimensional Molecular Structure

2000 • 418 citations

VolSurf: a new tool for the pharmacokinetic optimization of lead compounds

2000 • 417 citations

Correlation of Drug Absorption with Molecular Surface Properties

1996 • 408 citations

QSAR and 3D QSAR in drug design Part 1: methodology

1997 • 343 citations

Prediction of Human Intestinal Absorption of Drug Compounds from Molecular Structure

1998 • 341 citations

CYP3A4 drug interactions: correlation of 10 in vitro probe substrates

1999 • 326 citations

Evidence for two nonidentical drug-interaction sites in the human P-glycoprotein

1997 • 326 citations

HINT: A new method of empirical hydrophobic field calculation for CoMFA

1991 • 325 citations

New hydrogen-bond potentials for use in determining energetically favorable binding sites on molecules of known structure

1989 • 319 citations

Stimulation of P‐glycoprotein‐mediated drug transport by prazosin and progesterone

1999 • 299 citations

QSAR Model for Drug Human Oral Bioavailability

2000 • 297 citations

An alternative method for the alignment of molecular structures: Maximizing electrostatic and steric overlap

1990 • 283 citations

HT29-MTX/Caco-2 Cocultures as an in Vitro Model for the Intestinal Epithelium: In Vitro–in Vivo Correlation with Permeability Data from Rats and Humans

1996 • 258 citations

Linear correlation of the fraction of oral dose absorbed of 64 drugs between humans and rats.

1998 • 256 citations

Computational methods for the structural alignment of molecules.

2000 • 255 citations

Essential features of the P-glycoprotein pharmacophore as defined by a series of reserpine analogs that modulate multidrug resistance.

1989 • 233 citations

P-Glycoprotein Substrates and Antagonists Cluster into Two Distinct Groups

1997 • 229 citations

Comparative molecular field analysis (CoMFA). 2. Toward its use with 3D-structural databases

1990 • 215 citations

Evaluation of Dynamic Polar Molecular Surface Area as Predictor of Drug Absorption: Comparison with Other Computational and Experimental Predictors

1998 • 206 citations

Ligand-Based Identification of Environmental Estrogens

1996 • 205 citations

Intestinal transport of beta-lactam antibiotics: analysis of the affinity at the H+/peptide symporter (PEPT1), the uptake into Caco-2 cell monolayers and the transepithelial flux.

1999 • 202 citations

V.—On the Connection between Chemical Constitution and Physiological Action. Part. I.—On the Physiological Action of the Salts of the Ammonium Bases, derived from Strychnia, Brucia, Thebaia, Codeia, Morphia, and Nicotia

1868 • 201 citations

Estimation of Caco‐2 Cell Permeability using Calculated Molecular Descriptors

1996 • 200 citations

Drug liposome partitioning as a tool for the prediction of human passive intestinal absorption.

1999 • 200 citations

Computation of Brain−Blood Partitioning of Organic Solutes via Free Energy Calculations

1996 • 199 citations

Prediction of the Brain−Blood Distribution of a Large Set of Drugs from Structurally Derived Descriptors Using Partial Least-Squares (PLS) Modeling

1999 • 199 citations

Design principles for orally bioavailable drugs

1996 • 198 citations

ALADDIN: An integrated tool for computer-assisted molecular design and pharmacophore recognition from geometric, steric, and substructure searching of three-dimensional molecular structures

1989 • 188 citations

Integration of in Vitro Data into Allometric Scaling to Predict Hepatic Metabolic Clearance in Man: Application to 10 Extensively Metabolized Drugs

1997 • 177 citations

Competition of Hydrophobic Peptides, Cytotoxic Drugs, and Chemosensitizers on a Common P-glycoprotein Pharmacophore as Revealed by Its ATPase Activity

1996 • 176 citations

Compass: Predicting Biological Activities from Molecular Surface Properties. Performance Comparisons on a Steroid Benchmark

1994 • 170 citations

Pharmacokinetic Profiling in Drug Research: Biological, Physicochemical, and Computational Strategies

2006 • 166 citations

Novel Approach To Predicting P450-Mediated Drug Metabolism: Development of a Combined Protein and Pharmacophore Model for CYP2D6

1999 • 157 citations

Minimal Molecular Determinants of Substrates for Recognition by the Intestinal Peptide Transporter

1998 • 148 citations

Three-dimensional QSAR of human immunodeficiency virus (I) protease inhibitors. 1. A CoMFA study employing experimentally-determined alignment rules

1993 • 148 citations

Development of a pharmacophore for inhibition of human liver cytochrome P-450 2D6: molecular modeling and inhibition studies

1993 • 143 citations

Genomic Biology

2000 • 143 citations

Predicting human oral bioavailability of a compound: development of a novel quantitative structure-bioavailability relationship.

2000 • 136 citations

Comparative Molecular Field Analysis Using GRID Force-Field and GOLPE Variable Selection Methods in a Study of Inhibitors of Glycogen Phosphorylase b

1994 • 135 citations

Molecular Factors Influencing Drug Transfer across the Blood-Brain Barrier

1997 • 131 citations

Co-operative, competitive and non-competitive interactions between modulators of P-glycoprotein

1996 • 130 citations

QSAR in drug design and toxicology

1987 • 129 citations

Bile Acid Sequestrants

1990 • 128 citations

Theoretical Calculation and Prediction of Brain–Blood Partitioning of Organic Solutes Using MolSurf Parametrization and PLS Statistics

1998 • 124 citations

Absorption of Peptide and Peptidomimetic Drugs

1994 • 122 citations

Predicting the cytochrome P450 mediated metabolism of xenobiotics

1993 • 119 citations

Three- and four-dimensional quantitative structure activity relationship analyses of cytochrome P-450 3A4 inhibitors.

1999 • 119 citations

Three-dimensional-quantitative structure activity relationship analysis of cytochrome P-450 3A4 substrates.

1999 • 118 citations

How to Make Drugs Orally Active: A Substrate Template for Peptide Transporter PepT1

2000 • 116 citations

Substrate specificity of the ileal and the hepatic Na+/bile acid cotransporters of the rabbit. I. Transport studies with membrane vesicles and cell lines expressing the cloned transporters

1999 • 114 citations

Reversal of multidrug resistance by phenothiazines and structurally related compounds

1992 • 114 citations

Development of predictive pharmacokinetic simulation models for drug discovery

2000 • 112 citations

The importance of a nitrogen atom in modulators of multidrug resistance.

1999 • 109 citations

Virtual screening of intestinal drug permeability

2000 • 108 citations

Quantitative Relationships Between Lipophilic Character and Drug Metabolism

1972 • 106 citations

The use of human hepatocytes to select compounds based on their expected hepatic extraction ratios in humans.

1997 • 106 citations

Three-dimensional structure-activity relationships

1988 • 102 citations

Use of physiologically based pharmacokinetic modeling to investigate individual versus population risk

1996 • 99 citations

Three- and four-dimensional-quantitative structure activity relationship (3D/4D-QSAR) analyses of CYP2C9 inhibitors.

2000 • 95 citations

Three-dimensional quantitative structure activity relationship analyses of substrates for CYP2B6.

1999 • 93 citations

Molecular dynamics study of time-correlated protein domain motions and molecular flexibility: cytochrome P450BM-3

1997 • 93 citations

Theoretical calculation and prediction of intestinal absorption of drugs in humans using MolSurf parametrization and PLS statistics

1999 • 92 citations

Different approaches toward an automatic structural alignment of drug molecules: Applications to sterol mimics, thrombin and thermolysin inhibitors

1994 • 92 citations

Substrate specificity of the ileal and the hepatic Na+/bile acid cotransporters of the rabbit. II. A reliable 3D QSAR pharmacophore model for the ileal Na+/bile acid cotransporter

1999 • 92 citations

A Refined 3-Dimensional QSAR of Cytochrome P450 2C9: Computational Predictions of Drug Interactions

2000 • 89 citations

Molecular Modeling of Phenothiazines and Related Drugs As Multidrug Resistance Modifiers: A Comparative Molecular Field Analysis Study

1998 • 88 citations

Three-dimensional quantitative structure-activity relationship for inhibitors of cytochrome P4502C9.

1996 • 87 citations

Structural requirements for activity of propafenone-type modulators in P-glycoprotein-mediated multidrug resistance.

1996 • 87 citations

Structural Forms of Phenprocoumon and Warfarin That Are Metabolized at the Active Site of CYP2C9

1999 • 86 citations

Three and four dimensional-quantitative structure activity relationship (3D/4D-QSAR) analyses of CYP2D6 inhibitors.

1999 • 84 citations

Quinolone antibacterial agents: relationship between structure and in vitro inhibition of the human cytochrome P450 isoform CYP1A2.

1993 • 84 citations

Inhibition of Monoamine Oxidase-B by Condensed Pyridazines and Pyrimidines: Effects of Lipophilicity and Structure−Activity Relationships

1998 • 83 citations

Predicting drug absorption from molecular surface properties based on molecular dynamics simulations.

1998 • 79 citations

Structural characteristics of compounds that modulate P-glycoprotein-associated multidrug resistance

1990 • 78 citations

Structure–activity relationship studies of propafenone analogs based on P-glycoprotein ATPase activity measurements

1999 • 77 citations

The Virtual Cell

1998 • 76 citations

Structure-Related Inhibition of Human Hepatic Caffeine N3-Demethylation by Naturally Occurring Flavonoids

1998 • 76 citations

Combining in Vitro and in Vivo Pharmacokinetic Data for Prediction of Hepatic Drug Clearance in Humans by Artificial Neural Networks and Multivariate Statistical Techniques

1999 • 76 citations

Theoretical calculation and prediction of P-glycoprotein-interacting drugs using MolSurf parametrization and PLS statistics

2000 • 75 citations

Quantitative Structure-Activity Relationships of Cytochrome P-450

1993 • 73 citations

Characterization of binding properties to human P-glycoprotein: development of a [3H]verapamil radioligand-binding assay.

1999 • 72 citations

Autoactivation and activation of the cytochrome P450s.

1998 • 72 citations

3D-QSAR: a current perspective

1995 • 70 citations

Putative active site template model for cytochrome P4502C9 (tolbutamide hydroxylase).

1996 • 66 citations

A Refined Substrate Model for Human Cytochrome P450 2D6

1997 • 66 citations

Molecular Determinants of MAO Selectivity in a Series of Indolylmethylamine Derivatives: Biological Activities, 3D-QSAR/CoMFA Analysis, and Computational Simulation of Ligand Recognition

2000 • 66 citations

Prediction of the intestinal absorption of endothelin receptor antagonists using three theoretical methods of increasing complexity.

1999 • 65 citations

Glucuronidation of drugs by hepatic microsomes derived from healthy and cirrhotic human livers.

1999 • 63 citations

How does P-glycoprotein recognize its substrates?

1998 • 63 citations

Molecular Hashkeys: A Novel Method for Molecular Characterization and Its Application for Predicting Important Pharmaceutical Properties of Molecules

1999 • 63 citations

Three-dimensional quantitative structure-activity relationships of steroid aromatase inhibitors

1996 • 60 citations

Three-dimensional quantitative structure activity relationship computational approaches for prediction of human in vitro intrinsic clearance.

2000 • 57 citations

Identification of the cytochrome P450 enzymes involved in the metabolism of cisapride: in vitro studies of potential co‐medication interactions

2000 • 57 citations

Molecular basis of P450 inhibition and activation: implications for drug development and drug therapy.

1998 • 56 citations

Transport and metabolic characterization of Caco-2 cells expressing CYP3A4 and CYP3A4 plus oxidoreductase.

1999 • 56 citations

Quantitative Structure-Activity Relationships in Substrates, Inducers, and Inhibitors of Cytochrome P4501 (CYP1)

1997 • 55 citations

Modeling the cytochrome P450-mediated metabolism of chlorinated volatile organic compounds.

1996 • 55 citations

Molecular Determinants of Recognition for the Intestinal Peptide Carrier

1997 • 55 citations

A General Approach for the Prediction of the Intestinal Absorption of Drugs: Regression Analysis Using the Physicochemical Properties and Drug–Membrane Electrostatic Interaction

1998 • 54 citations

Affinities at the verapamil binding site of MDR1-encoded P-glycoprotein: drugs and analogs, stereoisomers and metabolites

2000 • 53 citations

On the Connection between Chemical Constitution and Physiological Action

1886 • 52 citations

Molecular modeling of the intestinal bile acid carrier: a comparative molecular field analysis study.

1997 • 50 citations

Commercial toxicology prediction systems: a regulatory perspective

1998 • 48 citations

Flexibility and stability of the structure of cytochromes P450 3A4 and BM‐3

2000 • 47 citations

The Use of Humanin VitroMetabolic Parameters to Explore the Risk Assessment of Hazardous Compounds: The Case of Ethylene Dibromide

1997 • 46 citations

Human and rat liver phenol sulfotransferase: structure-activity relationships for phenolic substrates.

1987 • 45 citations

Structure−Property Model for Membrane Partitioning of Oligopeptides

1999 • 43 citations

[36] Predicting the rates and regioselectivity of reactions mediated by the P450 superfamily

1996 • 42 citations

Structure-activity relationship of carbacephalosporins and cephalosporins: antibacterial activity and interaction with the intestinal proton-dependent dipeptide transport carrier of Caco-2 cells

1997 • 40 citations

Diversity Measures for Enhancing ADME Admissibility of Combinatorial Libraries

2000 • 39 citations

A Combined Hansch/Free-Wilson Approach as Predictive Tool in QSAR Studies on Propafenone-Type Modulators of Multidrug Resistance

1998 • 39 citations

Inhibition of Monoamine Oxidase by Pirlindole Analogues: 3D-QSAR and CoMFA Analysis

1998 • 38 citations

Molecular modeling study of structural requirements for the oligopeptide transporter

1996 • 38 citations

A New Set of Principal Properties for Heteroaromatics Obtained by GRID

1996 • 36 citations

Synthesis and Biological Activity of Bile Acid-Derived HMG-CoA Reductase Inhibitors. The Role of 21-Methyl in Recognition of HMG-CoA Reductase and the Ileal Bile Acid Transport System

1994 • 36 citations

Hydrophobicity of HIV protease inhibitors by immobilized artificial membrane chromatography: application and significance to drug transport.

1998 • 35 citations

A return to rational drug discovery: computer-based models of cells, organs and systems in drug target identification

2000 • 34 citations

QSAR and Molecular Modelling of Catamphiphilic Drugs Able to Modulate Multidrug Resistance in Tumors

1997 • 34 citations

Mapping the binding site of the small intestinal peptide carrier (PepT1) using comparative molecular field analysis.

1998 • 34 citations

A structure-function relationship among reserpine and yohimbine analogues in their ability to increase expression of mdr1 and P-glycoprotein in a human colon carcinoma cell line.

1995 • 33 citations

Qsar of P450 Oxidation: On the Value of Comparingk_catandK_mwithK_cat/K_m

1996 • 28 citations

A Comparative Molecular Field Analysis of Propafenone-type Modulators of Cancer Multidrug Resistance

1998 • 27 citations

Application of neural networks for the prediction of human pharmacokinetic parameters.

1995 • 26 citations

Molecular Field-Derived Descriptors for the Multivariate Modeling of Pharmacokinetic Data

2000 • 24 citations

Representing metabolic pathway information: an object-oriented approach.

1998 • 22 citations

Application of MS-WHIM Descriptors: 3. Prediction of Molecular Properties

2000 • 21 citations

Prediction of Drug Permeability Based onGrid Calculations

1999 • 19 citations

Extension of a predictive substrate model for human cytochrome P4502D6

1997 • 19 citations

Blood–brain barrier properties of human immunodeficiency virus antiretrovirals

1999 • 19 citations

Comparative Molecular Field Analysis of Compounds with CYP2A5 Binding Affinity

1995 • 18 citations

The design and molecular modeling of CNS drugs.

1999 • 17 citations

The hypocholesterolemic action of TA-7552 and its effects on cholesterol metabolism in the rat

1994 • 10 citations

AM1-based model system for estimation of brain / blood concentration ratios

1996 • 9 citations

ChemInform Abstract: Studies on Propafenone-Type Modulators of Multidrug Resistance. Part 8. Synthesis and Pharmacological Activity of Indanone Analogues.

1999 • 4 citations

VolSurf and its interest in structure-disposition relations.

2001 • 2 citations

Deleted Work

1955 • 0 citations