Concepts of Artificial Intelligence for Computer-Assisted Drug Discovery

Concepts of Artificial Intelligence for Computer-Assisted Drug Discovery

Authors: Yang X, Wang Y, Byrne R, Schneider G, Yang S
Publication: Chem Rev
Keywords: AI-assisted drug discovery and design, artificial intelligence, artificial intelligence (AI) modeling program
Software: ADMET Predictor®

Artificial intelligence (AI), and, in particular, deep learning as a subcategory of AI, provides opportunities for the discovery and development of innovative drugs.

1-Methyl-1,2,3,4-tetrahydroisoquinoline – The toxicological research on an exo/endogenous amine with antidepressant-like activity – In vivo, in vitro and in silico studies

1-Methyl-1,2,3,4-tetrahydroisoquinoline – The toxicological research on an exo/endogenous amine with antidepressant-like activity – In vivo, in vitro and in silico studies

Authors: Mozden E, Babinska I, Wojcikowski J, Antkiewicz -Michaluk L
Publication: Pharmacological Reports
Keywords: 1-Methyl-1, 2, 3, 4-tetrahydroisoquinoline, ADMET Predictor, antidepressant, Histopathology, in vivo–in silico predictions, Toxicity
Software: ADMET Predictor®

1-Methyl-1,2,3,4-tetrahydroisoquinoline (1MeTIQ) demonstrates significant neuroprotective activity.

A repository of protein abundance data of drug metabolizing enzymes and transporters for applications in physiologically based pharmacokinetic (PBPK) modelling and simulation

A repository of protein abundance data of drug metabolizing enzymes and transporters for applications in physiologically based pharmacokinetic (PBPK) modelling and simulation

Authors: Ladumor MK, Thakur A, Sharma SS, Rachapally A, Mishra S, Bobe P, Rao VK, Pammi P, Levi D, Balhara A, Ghandikota S, Joshi A, Nautiyal V, Prasad B, Singh S
Publication: Sci Rep
Keywords: enzyme ontogeny, mechanistic absorption model, PBPK modeling, population simulations
Software: GastroPlus®

Population factors such as age, gender, ethnicity, genotype and disease state can cause inter-individual variability in pharmacokinetic (PK) profile of drugs.

Integration of In Silico Pharmacokinetic Modeling Approaches Into In Vitro Dissolution Profiles to Predict Bioavailability of a Poorly Soluble Compound

Integration of In Silico Pharmacokinetic Modeling Approaches Into In Vitro Dissolution Profiles to Predict Bioavailability of a Poorly Soluble Compound

Authors: Kato T, Watanabe T, Nakamura K, Ando S
Publication: J Pharm Sci
Keywords: formulation screening, in vitro dissolution kinetics, mechanistic absorption model, pbbm, pbpk modeling and simulation, physiologically based biopharmaceutics modeling
Software: GastroPlus®

The objective of present study is to develop pharmacokinetic (PK) prediction methods using in silico PK model for oral immediate release drug products (i.e. solution, suspension, and amorphous solid dispersion).

Reactivation potency of two novel oximes (K456 and K733) against paraoxon-inhibited acetyl and butyrylcholinesterase: In silico and in vitro models

Reactivation potency of two novel oximes (K456 and K733) against paraoxon-inhibited acetyl and butyrylcholinesterase: In silico and in vitro models

Authors: Iqbal A, Malika S, Nurulain SM, Musilek K, Kuca K, Kalasz H, Fatmia MQ
Publication: Chem Biol Interact
Keywords: admet predictor, in silico, in vitro, reactivation, Toxicity
Software: ADMET Predictor®

Organophosphates (OPs) irreversibly inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) enzymes.

Verubecestat Pharmacokinetic and Exposure-Response Results From APECS, a Phase 3 Trial in Prodromal Alzheimer’s Disease

Verubecestat Pharmacokinetic and Exposure-Response Results From APECS, a Phase 3 Trial in Prodromal Alzheimer’s Disease

Authors: Stone J, Kleijn H, Jaworowicz DJ, Passarell JA, Dockendorf M, Xu M, Rasmussen C, Humphrey RL, Voss T, Egan M
Publication: Alzheimer’s & Dementia
Keywords: APECS, BACE inhibitor, exposure-response, MK-8931, pharmacokinetic, verubecestat
Division: Clinical Pharmacology and Pharmacometrics (CPP)

The BACE inhibitor verubecestat (MK-8931) demonstrated cognitive and functional decline relative to placebo in a 2-year Phase 3 trial of individuals with prodromal AD (APECS; NCT01953601), along with...

In silico Tools at Early Stage of Pharmaceutical Development: Data Needs and Software Capabilities

In silico Tools at Early Stage of Pharmaceutical Development: Data Needs and Software Capabilities

Authors: Njoku JO, Amaral Silva D, Mukherjee D, Webster GK, Löbenberg R
Publication: AAPS PharmSciTech
Keywords: admet predictor, dddplus, dissolution, dissolution method development, in vitro dissolution, mechanistic dissolution model, model fitting, product specifications, simulation
Software: ADMET Predictor®, DDDPlus™, GastroPlus®

In early drug development, the selection of a formulation platform and decisions on formulation strategies have to be made within a short timeframe and often with minimal use of the active pharmaceutical ingredient (API).

Towards a TREK-1/2 (TWIK-Related K+ Channel 1 and 2) dual activator tool compound: Multi-dimensional optimization of BL-1249

Towards a TREK-1/2 (TWIK-Related K+ Channel 1 and 2) dual activator tool compound: Multi-dimensional optimization of BL-1249

Authors: Iwaki Y, Yashiro K, Kokubo M, Mori T, Wieting JM, McGowan KM, Bridges TM, Engers DW, Denton JS, Kurata H, Lindsley CW
Publication: Bioorg Med Chem Lett.
Keywords: Activator, K2P channel, Potassium ion channel, TREK-1, TREK-2
Software: ADMET Predictor®

This letter describes a focused, multi-dimensional optimization campaign around BL-1249, a fenamate class non-steroidal anti-inflammatory and a known activator of the K2P potassium channels TREK-1 (K2P2.1) and TREK-2 (K2P10.1).

Computational Model To Predict the Fraction of Unbound Drug in the Brain

Computational Model To Predict the Fraction of Unbound Drug in the Brain

Authors: Esaki T, Ohashi R, Watanabe R, Natsume-Kitatani Y, Kawashima H, Nagao C, Mizuguchi K
Publication: J Chem Inf Model
Keywords: brain drug effects, central nervous system, in silico, Toxicity
Software: ADMET Predictor®

Knowing the value of the unbound drug fraction in the brain (fu,brain) is essential in estimating its effects and toxicity on the central nervous system (CNS)...

Novel isoxazole derivatives as potential antiparkinson agents: synthesis, evaluation of monoamine oxidase inhibitory activity and docking studies

Novel isoxazole derivatives as potential antiparkinson agents: synthesis, evaluation of monoamine oxidase inhibitory activity and docking studies

Authors: Agrawal NG, Mishra P
Publication: Med Chem Res
Keywords: Carbohydrazide, Isoxazole, MAO-B inhibitor, Neurodegenerative diseases, Parkinson's disease
Software: ADMET Predictor®

Selective monoamine oxidase B inhibitors are potential drug candidates for the treatment of Parkinson’s disease.

Computational Systems Pharmacology-Target Mapping for Fentanyl-Laced Cocaine Overdose

Computational Systems Pharmacology-Target Mapping for Fentanyl-Laced Cocaine Overdose

Authors: Cheng J, Wang S, Lin W, Wu N, Wang Y, Chen M, Xie X, Feng Z
Publication: ACS Chem Neurosci
Keywords: cocaine, computational systems pharmacology-target mapping, Fentanyl, fentanyl-laced cocaine, heroin, opioid, overdose, polydrug addiction
Software: ADMET Predictor®

The United States of America is fighting against one of its worst-ever drug crises.

Requirements to Establishing Confidence in Physiologically Based Pharmacokinetic (PBPK) Models and Overcoming Some of the Challenges to Meeting Them

Requirements to Establishing Confidence in Physiologically Based Pharmacokinetic (PBPK) Models and Overcoming Some of the Challenges to Meeting Them

Authors: Peters SA, Dolgos H
Publication: Clin Pharmacokinet
Keywords: mechanistic absorption model, model validation, PBPK modeling, population predictions, regulatory interaction
Software: GastroPlus®

When scientifically well-founded, the mechanistic basis of physiologically based pharmacokinetic (PBPK) models can help reduce the uncertainty and increase confidence in extrapolations outside the studied scenarios or studied populations.