Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria

Discovery and Preclinical Pharmacology of INE963, a Potent and Fast-Acting Blood-Stage Antimalarial with a High Barrier to Resistance and Potential for Single-Dose Cures in Uncomplicated Malaria

Authors: Taft BR, Yokokawa F, Kirrane T, Mata AC, Huang R, Blaquiere N, Waldron G, Zou B, Simon O, Vankadara S, Chan WL, Ding M, Sim S, Straimer J, Guiguemde A, Lakshminarayana SB, Jain JP, Bodenreider C, Thompson C, Lanshoeft C, Shu W, Fang E, Qumber J, Chan K, Pei L, Chen YL, Schulz H, Abas SN, Ang X, Liu Y, Angulo-Barturen I, Jimenez-Diaz MB, Gamo, FJ, Crespo-Fernandez B, Rosenthal PJ, Tumwebaze P, Cooper RA, Campo B, Campbell S, Wagner J, Diagana TT, Sarko C
Publication: J Med Chem
Keywords: dose selection, fih, gastroplus, machine learning, mechanistic absorption, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

A series of 5-aryl-2-amino-imidazothiadiazole (ITD) derivatives were identified by a phenotype-based high-throughput screening using a blood stage Plasmodium falciparum (Pf) growth inhibition assay.

High-Throughput Screening for Extracellular Inhibitors of the FLT3 Receptor Tyrosine Kinase Reveals Chemically Diverse and Druggable Negative Allosteric Modulators

High-Throughput Screening for Extracellular Inhibitors of the FLT3 Receptor Tyrosine Kinase Reveals Chemically Diverse and Druggable Negative Allosteric Modulators

Authors: Hany R, Leyris JP, Bret G, Mallié S, Sar C, Thouaye M, Hamze A, Provot O, Sokoloff P, Valmier J, Rognan D
Publication: ACS Chem Bio
Keywords: Fluorescence, inhibition, inhibitors, Peptides and proteins, receptors
Software: ADMET Predictor®
Therapeutic Areas: Oncology

Inhibiting receptor tyrosine kinases is commonly achieved by two main strategies targeting either the intracellular kinase domain by low molecular weight compounds or...

In vivo neurophysiological assessment of in silico predictions of neurotoxicity: Citronellal, 3,4-dichloro-1-butene, and benzyl bromoacetate

In vivo neurophysiological assessment of in silico predictions of neurotoxicity: Citronellal, 3,4-dichloro-1-butene, and benzyl bromoacetate

Authors: Jung GL, McDaniel KL, LoPachin RM, Geohagen BC, Smith A, Huffstickler M, Herr DW
Publication: Neurotoxicology
Keywords: animal testing, gastroplus, mechanistic absorption, pbk, PBPK modeling, pbtk, risk assessment, safety exposure, Toxicity
Software: GastroPlus®

Neurotoxicants may be widespread in the environment and can produce serious health impacts in the human population.

Clinical Pharmacokinetics and Pharmacodynamics of Esaxerenone, a Novel Mineralocorticoid Receptor Antagonist: A Review

Clinical Pharmacokinetics and Pharmacodynamics of Esaxerenone, a Novel Mineralocorticoid Receptor Antagonist: A Review

Authors: Janković SM, Jankovic SV
Publication: Eur J Drug Metab Pharmacokinet
Keywords: ddI, Drug-drug interactions, fih, first-in-human, gastroplus, gut metabolism, IVIVE, mechanistic absorption, PBPK modeling, physiologically based pharmacokinetics
Software: GastroPlus®

Esaxerenone is a selective, nonsteroidal, high-affinity mineralocorticoid receptor antagonist recently approved in Japan for the treatment of hypertension.

Potent Neutralization of Omicron and other SARS-CoV-2 Variants of Concern by Biparatopic Human VH Domains

Potent Neutralization of Omicron and other SARS-CoV-2 Variants of Concern by Biparatopic Human VH Domains

Authors: Chen C, Martinez DR, Marti MM, Schafer A, Cheng MH, Mannar D, Zhu X, Banerjee A, Sobolewski MD, Kim A, Treat BR, Castanha PMS, Enick N, McCormick KD, Liu X, Adams C, Hines MG, Sun Z, Chen W, Jacobs JL, Barratt-Boyes S, Mellors JW, Baric R, Bahar I, Dimitrov D, Subramaniam S, Saville J, Li W
Publication: bioRxiv
Keywords: biparatopic antibody, COVID-19, Omicron variant, SARS-CoV-2

The emergence of SARS-CoV-2 variants of concern (VOCs) requires the development of next-generation biologics that are effective against a variety of strains of the virus.

Post-Approval/Generics Track Poster Presentation: Use of PBBM to Establish Dissolution Safe Space via IVIVR for Concor®

Post-Approval/Generics Track Poster Presentation: Use of PBBM to Establish Dissolution Safe Space via IVIVR for Concor®

Authors: Macwan J
Conference: SLP MIDD+
Keywords: Concor, MIDD (model-informed drug development), MIDD+ 2022, modeling and simulation, pbbm, PBBM modeling, Post-Approval/Generics Track, SLP MIDD+ Virtual Conference, SLP2022MIDD
Division: PBPK

Presented by Joyce Macwan at SLP MIDD+ Virtual Conference February 16th-17th, 2022

Post-Approval/Generics Track Poster Presentation: Relationship between Pimavanserin Exposure and QTc Interval in Patients with Schizophrenia: Modelling Analysis from Randomized, Double-Blind, Placebo-Controlled Studies

Post-Approval/Generics Track Poster Presentation: Relationship between Pimavanserin Exposure and QTc Interval in Patients with Schizophrenia: Modelling Analysis from Randomized, Double-Blind, Placebo-Controlled Studies

Authors: Huang H
Conference: SLP MIDD+
Keywords: MIDD (model-informed drug development), MIDD+ 2022, modeling and simulation, pimavanserin, Placebo-Controlled Studies, Post-Approval/Generics Track, QTc, schizophrenia, SLP MIDD+ Virtual Conference, SLP2022MIDD
Division: PBPK

Presented by Hannah Huang at SLP MIDD+ Virtual Conference February 16th-17th, 2022

Post-Approval/Generics Track Poster Presentation: Therapeutic Drug Monitoring for Tyrosine Kinase Inhibitors. Possibilities, difficulties, and challenges

Post-Approval/Generics Track Poster Presentation: Therapeutic Drug Monitoring for Tyrosine Kinase Inhibitors. Possibilities, difficulties, and challenges

Authors: Chauvin J
Conference: SLP MIDD+
Keywords: MIDD (model-informed drug development), MIDD+ 2022, modeling and simulation, Post-Approval/Generics Track, SLP MIDD+ Virtual Conference, SLP2022MIDD, therapeutic drug monitoring, Tyrosine Kinase Inhibitors
Division: PBPK

Presented by Jonathan Chauvin at SLP MIDD+ Virtual Conference February 16th-17th, 2022

Clinical Track: Yo-Yo Dieting Predicted to Contribute to Fibrosis Score Reductions in Untreated (Placebo) Cohorts

Clinical Track: Yo-Yo Dieting Predicted to Contribute to Fibrosis Score Reductions in Untreated (Placebo) Cohorts

Authors: Shoda LKM
Conference: SLP MIDD+
Keywords: Clinical Track, MIDD (model-informed drug development), MIDD+ 2022, modeling and simulation, SLP MIDD+ Virtual Conference, SLP2022MIDDConference: SLP MIDD+, untreated cohorts, yo-yo dieting
Division: PBPK

Presented by Lisl Shoda at SLP MIDD+ Virtual Conference February 16th-17th, 2022