Discovery of ASP5878: Synthesis and structure–activity relationships of pyrimidine derivatives as pan-FGFRs inhibitors with improved metabolic stability and suppressed hERG channel inhibitory activity

Discovery of ASP5878: Synthesis and structure–activity relationships of pyrimidine derivatives as pan-FGFRs inhibitors with improved metabolic stability and suppressed hERG channel inhibitory activity

Authors: Kuriwaki I, Kameda M, Iikubo K, Hisamichi H, Kawamoto Y, Kikuchi S, Moritomo H, Terasaka T, Iwai Y, Noda A, Tomiyama H, Kikuchi A, Hirano M
Publication: Bioorg Med Chem
Keywords: Bladder cancer, Brain Penetration, Fibroblast growth factor receptor 3, hERG channel, metabolic stability, Pharmacokinetic study, structure activity relationships, Telemetry study
Software: ADMET Predictor®
Therapeutic Areas: Oncology

Fibroblast growth factor receptor 3 (FGFR3) is an attractive therapeutic target for the treatment of bladder cancer patients harboring genetic alterations in FGFR3.

Estrogenic Activity of Tetrazole Derivatives Bearing Bisphenol Structures: Computational Studies, Synthesis, and In Vitro Assessment

Estrogenic Activity of Tetrazole Derivatives Bearing Bisphenol Structures: Computational Studies, Synthesis, and In Vitro Assessment

Authors: Gadgoli UB, Kumar S, Kumar D, Pai M, Pulya S, Ghosh B, Kulkarni OP
Publication: J Chem Inf Model
Keywords: Aromatic compounds, Bisphenols, Electrostatics, ligands, Metabolic, Screening assays
Software: ADMET Predictor®

The classification of bisphenol A (BPA) as an industrial endocrine disruptor has led to a ban of this ubiquitous critical starting material from food and medical applications.

Predicting nonlinear relationships between external and internal concentrations with physiologically based pharmacokinetic modeling

Predicting nonlinear relationships between external and internal concentrations with physiologically based pharmacokinetic modeling

Authors: Hoer D, Barton HA, Paini A, Bartels M, Ingle B, Domoradzki J, Fisher J, Embry M, Villanueva P, Miller D, Zhang Q, Edwards SW, Tan YM
Publication: Toxicol Appl Pharmacol
Keywords: admet predictor, animal testing, chemicals, drug safety testing, gastroplus, Michaelis-Menten, nonlinear pk, PBPK modeling, risk assessment, toxicology

Although external concentrations are more readily quantified and often used as the metric for regulating and mitigating exposures to environmental chemicals, the toxicological response to an environmental chemical is more directly related to its internal concentrations than the external concentration.

A biologically based model to quantitatively assess the role of the nuclear receptors liver X (LXR), and pregnane X (PXR) on chemically induced hepatic steatosis

A biologically based model to quantitatively assess the role of the nuclear receptors liver X (LXR), and pregnane X (PXR) on chemically induced hepatic steatosis

Authors: Bay C, El-Masri HA
Publication: Toxicol Lett
Keywords: alternative animal testing, gastroplus, pbk modeling, PBPK modeling, physiologically based pharmacokinetics, risk assessment, safety assessment, toxicology
Software: GastroPlus®

Hepatic steatosis is characterized by the intracellular increase of free fatty acids (FFAs) in the form of triglycerides in hepatocytes.

Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, A Potential Oral Drug Candidate for COVID-19 Treatment

Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, A Potential Oral Drug Candidate for COVID-19 Treatment

Authors: Wang AQ, Hagen NR, Padilha EC, Yang M, Shah P, Chen CZ, Huang W, Terse P, Sanderson P, Zheng W, Xu X
Publication: bioRxiv
Keywords: dose slection, fih, FIHSimulator, first-in-human, gastroplus, IVIVE, mechanistic absorption, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

Preclinical pharmacokinetics (PK) and in vitro ADME properties of GS-441524, a potential oral agent for the treatment of Covid-19, were studied. GS-441524 was stable in vitro in liver microsomes, cytosols, and hepatocytes of mice, rats, monkeys, dogs, and humans.

Chlordecone: development of a physiologically based pharmacokinetic tool to support human health risks assessments

Chlordecone: development of a physiologically based pharmacokinetic tool to support human health risks assessments

Authors: Emond C, Multigner L
Publication: Arch Toxicol
Keywords: gastroplus, partition coefficients, PBPK modeling, safety assessment, toxicology
Software: GastroPlus®

Chlordecone (CD; Kepone™) is a carcinogenic organochlorine insecticide with neurological, reproductive, and developmental toxicity that was widely used in the French West Indies (FWI) from 1973 to 1993 to fight banana weevils.

Capturing Interpatient Variability with SimPops

Capturing Interpatient Variability with SimPops

Authors: Siler SQ
Conference: ASCPT
Keywords: AEC, CARDIOsym, clinical, clinical data, DILIsym, disease progression, DLCO, fibrosis, FVC, Genetic algorithms, honeycombing, HRCT, ILDsym, immune, IPFsym, KIDNEYsym, lung collagen, mediator, MITOsym, model, NAFLDsym, pathophysiology, pirfenidone, proteoglycan, quantitative systems pharmacology (QSP), Quantitative Systems Toxicology (QST), RENAsym, SimPops, treatment
Software: CARDIOsym, DILIsym®, ILDsym™, IPFsym®, KIDNEYsym, MITOsym®, NAFLDsym®, RENAsym®
Division: Quantitative Systems Pharmacology (QSP)

SimPops provide significant value for drug development. "The SimPops are the Crown Jewel".

Synthesis and Characterization of Novel 2-Pyridine Mono(thio)carbohydrazones as Promising Antioxidant and Antimicrobial Agents. Experimental and Theoretical Approach

Synthesis and Characterization of Novel 2-Pyridine Mono(thio)carbohydrazones as Promising Antioxidant and Antimicrobial Agents. Experimental and Theoretical Approach

Authors: Mrdan G, Tot A, Vranes M, Raseta M, Knežević P, Verbic T, Matijević BM
Publication: Experimental and Theoretical Approach
Keywords: biological activity, hydrazones, TD-DFT
Software: ADMET Predictor®
Therapeutic Areas: Anti-effective

Four new derivatives of 2-pyridine mono(thio)carbohydrazones were synthesized by condensation of carbaldehydes with carbohydrazide and thiocarbohydrazide following a known procedure.

Applications of PBPK/PBBM modeling in generic product development: An industry perspective

Applications of PBPK/PBBM modeling in generic product development: An industry perspective

Authors: Yuvaneshwari K, Kollipara S, Ahmed T, Chachad S
Publication: J Drug Deliv Sci Technol
Keywords: dissolution safe space, food effect, gastroplus, mechanistic absorption model, pbbm, PBPK modeling, physiologically based biopharmaceutics, vbe, virtual bioequivalence
Software: GastroPlus®

Physiologically based pharmacokinetic (PBPK) modeling and physiologically based biopharmaceutics modeling (PBBM) are invaluable tools with wide applications during drug discovery and development stages.

Assessment of the predictive capability of modelling and simulation to determine bioequivalence of inhaled drugs: A systematic review

Assessment of the predictive capability of modelling and simulation to determine bioequivalence of inhaled drugs: A systematic review

Authors: Rebello J, Brashier B, Shukla S
Publication: Daru Jour Pharma Sci
Keywords: gastroplus, inhaled dosing, PBPK modeling, pcat, physiologically based pharmacokinetics, population simulations, pulmonary modeling, pulmonary playlist, virtual bioequivalence
Software: GastroPlus®

There are a multitude of different modelling techniques that have been used for inhaled drugs.

Alternative experimental approaches to reduce animal use in biomedical studies

Alternative experimental approaches to reduce animal use in biomedical studies

Authors: Lee SY, Lee DY, Kang JH, Jeong JW, Kim JH, Kim HW, Oh DH, Kim JM, Rhim SJ, Kim GD, Kim HS, Jang YD, Park Y, Hura SJ
Publication: J Drug Deliv Sci Technol
Keywords: Alternative animal study, Biomedicine, in vitro models, Invertebrate model, Organ-on-a-chip
Software: ADMET Predictor®

We review experimental approaches that can be used instead of in vivo studies involving vertebrate animal models and human clinical trials.

Dose Number as a Tool to Guide Lead Optimization for Orally Bioavailable Compounds in Drug Discovery

Dose Number as a Tool to Guide Lead Optimization for Orally Bioavailable Compounds in Drug Discovery

Authors: Wuelfing WP, El Marrouni A, Lipert MP, Daublain P, Converso A, Templeton AC
Publication: J Med Chem
Keywords: formulation assessment, gastroplus, mechanistic absorption, pbbm, PBPK modeling, physiologically based biopharmaceutics
Software: GastroPlus®

Small molecule developability challenges have been well documented over the last two decades.