3D-QSAR, molecular docking and in silico ADMET studies of propiophenone derivatives with anti-HIV-1 protease activity

3D-QSAR, molecular docking and in silico ADMET studies of propiophenone derivatives with anti-HIV-1 protease activity

Authors: Jovanović M, Turković N, Ivkovic B, Vujić Z, Nikolic K, Grubišić S
Publication: Struct Chem
Keywords: computational ADME, computer-aided drug design, HIV/AIDS, HOMO-LUMO, molecular docking, proteases, quantitative structure-activity relationships (QSAR)
Software: ADMET Predictor®
Therapeutic Areas: Anti-effective

HIV protease inhibitors are one of the most important agents for the treatment of HIV infection.

Absence of Association Between Abatacept Exposure and Initial Infection in Patients With Juvenile Idiopathic Arthritis

Absence of Association Between Abatacept Exposure and Initial Infection in Patients With Juvenile Idiopathic Arthritis

Authors: Ruperto N, Brunner H, Tzaribachev N, Vega-Cornejo G, Louw I, Cimaz R, Dare J, Espada G, Faugier E, Ferrandiz M, Gerloni V, Quartier P, Silva CA, Wagner-Weiner L, Gandhi Y, Passarell JA, Nys M, Wong R, Martini A, Lovell DJ
Publication: J Rheumatol
Keywords: biological therapy, disease-modifying antirheumatic drugs, infection, juvenile idiopathic arthritis
Division: Clinical Pharmacology and Pharmacometrics (CPP)

To assess the relationship between infection risk and abatacept (ABA) exposure levels in patients with polyarticular-course juvenile idiopathic arthritis (pJIA) following treatment with

Impact of Daridorexant, a Dual Orexin Receptor Antagonist, on Cardiac Repolarization Following Bedtime Dosing: Results from a Thorough QT Study Using Concentration-QT Analysis

Impact of Daridorexant, a Dual Orexin Receptor Antagonist, on Cardiac Repolarization Following Bedtime Dosing: Results from a Thorough QT Study Using Concentration-QT Analysis

Authors: Schilling U, Henrich A, Muehlan C, Krause A, Dingemanse J, Ufer M
Publication: Clinical Drug Investigation
Keywords: cardiac repolarization, concentration-QT analysis, daridorexant, insomnia

Daridorexant is a new dual orexin receptor antagonist currently in late-stage clinical development for the treatment of insomnia.

Pharmacokinetic Profile of Pimavanserin in Patients With Dementia-Related Psychosis and Concomitant Acetylcholinesterase Inhibitor Use: Modeling Data From the Phase 3 HARMONY Study

Pharmacokinetic Profile of Pimavanserin in Patients With Dementia-Related Psychosis and Concomitant Acetylcholinesterase Inhibitor Use: Modeling Data From the Phase 3 HARMONY Study

Authors: Darwish M, Jaworowicz DJ, Owen JS, Brandt T, DeKarske D, Stankovic S
Conference: Alzheimers Association International Conference
Keywords: 5HT2A receptor, AChEI, HARMONY, NCT03325556, pharmacokinetic, pimavanserin, serotonin-modulating
Division: Clinical Pharmacology and Pharmacometrics (CPP)

Pimavanserin is a selective serotonin-modulating agent with inverse agonist/antagonist activity at the 5HT2A receptor, and to a lesser extent at...

Physiologically Based Pharmacokinetic Models Are Effective Support for Pediatric Drug Development

Physiologically Based Pharmacokinetic Models Are Effective Support for Pediatric Drug Development

Authors: Wang K, Jiang K, Wei X, Li Y, Wang T, song y
Publication: AAPS PharmSciTech
Keywords: children, dose selection, drug development, gastroplus, infants, mechanistic absorption, pbbm, PBPK model, PBPK modeling, pediatrics, physiologically based biopharmaceutics
Software: GastroPlus®

Pediatric drug development faces many difficulties. Traditionally, pediatric drug doses are simply calculated linearly based on the body weight, age, and body surface area of adults.

Multitask machine learning models for predicting lipophilicity (logP) in the SAMPL7 challenge

Multitask machine learning models for predicting lipophilicity (logP) in the SAMPL7 challenge

Authors: Lenselink EB, Stouten PFW
Publication: J Comput Aided Mol Des
Keywords: D-MPNN, logP prediction, Multitask machine learning, SAMPL7
Software: ADMET Predictor®

Accurate prediction of lipophilicity—logP—based on molecular structures is a well-established field. Predictions of logP are often used to drive forward drug discovery projects.

Development of rivaroxaban microemulsion-based hydrogel for transdermal treatment and prevention of venous thromboembolism

Development of rivaroxaban microemulsion-based hydrogel for transdermal treatment and prevention of venous thromboembolism

Authors: Araújo CDCB, Simon A, Honório TDS, Da Silva SVC, Valle IMM, Da Silva LCRP, Rodrigues CR, de Sousa VP, Cabral LM, Sathler PC, do Carmo FA
Publication: Colloids Surf B Biointerfaces
Keywords: Anticoagulant, dermal absorption, dermal delivery, dose optimization, gastroplus, mechanistic absorption, Microemulsion-based hydrogel, pbbm, PBPK modeling, physiologically based biopharmaceutics, Rivaroxaban, tcat, Transdermal delivery, Venous thromboembolism
Software: GastroPlus®

We have developed a microemulsion (ME)-based hydrogel, containing propylene glycol, Azone®, Labrasol®, isobutanol and water (20:3:18:3:56), for the transdermal delivery of rivaroxaban (RVX). Formulation ME-1:RVX...

Combination of a biopharmaceutic classification system and physiologically based pharmacokinetic models to predict absorption properties of baicalein in vitro and in vivo

Combination of a biopharmaceutic classification system and physiologically based pharmacokinetic models to predict absorption properties of baicalein in vitro and in vivo

Authors: Liu Y, Sun J, Zhong L, Li Y, Er AN, Li T, Yang L, Dong L
Publication: Journal of Traditional Chinese Medical Sciences
Keywords: Absorption properties, baicalein, BCS, biopharmaceutical classification system, Chinese herb, gastroplus, in situ intestinal perfusion, intrinsic dissolution rate, IVIVE, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics, physiologically based pharmacokinetics, plant-based
Software: ADMET Predictor®, GastroPlus®

To determine the in vitro and in vivo absorption properties of active ingredients of the Chinese medicine, baicalein, to enrich mechanistic understanding of oral drug absorption.

An insight into the anticancer potential of carbamates and thiocarbamates of 10-demethoxy-10-methylaminocolchicine

An insight into the anticancer potential of carbamates and thiocarbamates of 10-demethoxy-10-methylaminocolchicine

Authors: Krzywik J, Aminpour M, Maj E, Moshari M, Mozga W, Wietrzyk J, Tuszynski JA, Huczyńskia A
Publication: Eur J Med Chem
Keywords: anticancer agents, Carbamate, Crystal structure, Docking studies, QSAR, Thiocarbamate, Tubulin inhibitors
Software: ADMET Predictor®

Colchicine shows very high antimitotic activity, therefore, it is used as a lead compound for generation of new anticancer agents. In the hope of developing novel, useful drugs with more favourable pharmacological...

Model-based dose selection for the phase 3 evaluation of molnupiravir (MOV) in the treatment of COVID-19 in adults

Model-based dose selection for the phase 3 evaluation of molnupiravir (MOV) in the treatment of COVID-19 in adults

Authors: Chawla A, Cao Y, Stone J, Birger R, Sardella S, Wan H, Gaffney L, Therien A, Murgolo N, Painter W, Painter GR, Wayne H, Grobler JA, Rizk ML, Butterton JR, Johnson MG, Brown ML, Paschke A, De Anda C, Gao W
Conference: ECCMID
Keywords: COVID-19, molnupiravir (MOV), pharmacokinetics, SARS-CoV-2
Division: Clinical Pharmacology and Pharmacometrics (CPP)
Therapeutic Areas: Infectious Diseases

There is an urgent need for effective treatment options that are easily administered and readily implementable in health systems globally to reduce the impact of COVID-191

Cosmetics Europe evaluation of 6 in silico skin penetration models

Cosmetics Europe evaluation of 6 in silico skin penetration models

Authors: Grégoire S, Sorrell I, Lange D, Najjar A, Schepky A, Ellison C, Troutman J, Fabian E, Duplan H, Géniès C, Jacques-Jamin C, Klaric M, Hewitt NJ
Publication: Computational Toxicology
Keywords: dermal delivery, gastroplus, IVIVE, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics modeling, tcat, transdermal
Software: GastroPlus®

The ADME TF aims to develop in silico skin penetration models using in vitro human skin penetration data for 25 chemicals solubilized in water.

Predicting quantitatively P-glycoprotein mediated drug-drug interactions and intestinal absorption using humanized mice

Predicting quantitatively P-glycoprotein mediated drug-drug interactions and intestinal absorption using humanized mice

Authors: Miyake T, Tsutsui H, Haraya K, Tachibana T, Morimoto K, Takehara S, Ayabe M, Kazuki Y
Publication: Br J Pharmacol
Keywords: DDIs, gastroplus, IVIVE, pbbm, PBPK modeling, pgp, physiologically based biopharmaceutics modeling, transporters
Software: GastroPlus®

P-glycoprotein (P-gp) exhibits a broad specificity for substrates and affects their pharmacokinetics, especially intestinal absorption.

Predicting the potential toxicity of 26 components in Cassiae semen using in silico and in vitro approaches

Predicting the potential toxicity of 26 components in Cassiae semen using in silico and in vitro approaches

Authors: Yang J, Wang S, Zhang T, Sun Y, Han L, Banahene PO, Wang Q
Publication: Cur Res Tox
Keywords: Cassia obtusifolia L, Cassiae semen, cytotoxicity, general linear models (GLMs), QSAR model
Software: ADMET Predictor®, GastroPlus®

Cassiae semen are dried and ripe seeds of Cassia obtusifolia L. or Cassia tora L. (Fabaceae) and have been made into roasted tea or used as a traditional medicine in Asian countries.

Biocompatible solvent selection based on thermodynamic and computational solubility models, in-silico GastroPlus prediction, and cellular studies of ketoconazole for subcutaneous delivery

Biocompatible solvent selection based on thermodynamic and computational solubility models, in-silico GastroPlus prediction, and cellular studies of ketoconazole for subcutaneous delivery

Authors: Hussain A, Alshehri S, Ramzan M, Afzal O, Altamimi ASA, Alossaimi MA
Publication: J Drug Deliv Sci Technol
Keywords: dermal delivery, excipients, gastroplus, injection, pbbm, PBPK modeling, physiologically based biopharmaceutics modeling, subq
Software: GastroPlus®

We aimed to identify a suitable solvent [dimethyl acetamide (DMA), ethyl acetate, (EA), N-methyl pyrrolidone (NMP), cremophor-EL (CEL), transcutol-HP (THP), polyethylene glycol 400 (PEG-400), limonene and ethanol]...