Elias Carvalho Padilha

Structure–Activity Relationship Studies toward the Optimization of First-In-Class Selective Small Molecule Agonists of the GPCR Relaxin/Insulin-like Family Peptide Receptor 2

Kenneth J. Wilson, María Esteban-López, Courtney B. Myhr, Wenjuan Ye et autres

A dose–response quantitative high-throughput screening of 147,334 small molecule compounds using a human Relaxin/Insulin-like Family Peptide Receptor 2 (RXFP2)-transfected HEK293T-RXFP2 cell line identified compound 5 with modest Insulin-Like3 (INSL3) agonist activity. An extensive structure–activity relationship (SAR) study was undertaken to improve potency, …

us (code pays fourni par la source)

Screening towards a CYP3A7-specific marker reaction against CYP3A4 and CYP3A5

Elias Carvalho Padilha

us (code pays fourni par la source)

Amidino-rocaglates (ADRs), a class of synthetic rocaglates, are potent inhibitors of SARS-CoV-2 replication through inhibition of viral protein synthesis

Patrick T. Keiser, Wenhan Zhang, Michael Ricca, Alan Wacquiez et autres

us, ca (code pays fourni par la source)

Metabolism of DHED in vitro and in vivo to support drug optimization

Elias Carvalho Padilha

us (code pays fourni par la source)

Development and validation of PAMPA-BBB QSAR model to predict brain penetration potential of novel drug candidates

Rintaro Kato, Wenyu Zeng, Vishal B. Siramshetty, J. W. Williams et autres

Efficiently circumventing the blood-brain barrier (BBB) poses a major hurdle in the development of drugs that target the central nervous system. Although there are several methods to determine BBB permeability of small molecules, the Parallel Artificial Membrane Permeability Assay (PAMPA) is one …

us (code pays fourni par la source)

Automated measurement of transepithelial electrical resistance (TEER) in 96-well transwells using ECIS TEER96: Single and multiple time point assessments

Pranav Shah, Charles R. Keese, Michael F. Detweiler, Sam Michael et autres

Transepithelial electrical resistance (TEER) is a widely used technique for quantifying the permeability of epithelial and endothelial cell layers. However, traditional methods of measuring TEER are limited to single timepoint measurements and can subject cells to an altered environment during the measurement. …

us (code pays fourni par la source)

In vitro and in vivo pharmacokinetic characterization, chiral conversion and PBPK scaling towards human PK simulation of S-MRI-1867, a drug candidate for Hermansky-Pudlak syndrome pulmonary fibrosis

Elias Carvalho Padilha, Mengbi Yang, Pranav Shah, Amy Q. Wang et autres

Hermansky-Pudlak syndrome (HPS) is a rare autosomal recessive disorder that affects lysosome-related organelles, often leading to fatal pulmonary fibrosis (PF). The search for a treatment for HPS pulmonary fibrosis (HPSPF) is ongoing. S-MRI-1867, a dual cannabinoid receptor 1 (CB1R)/inducible nitric oxide synthase …

us, ca (code pays fourni par la source)

Consideration of vendor-related differences in hepatic metabolic stability data to optimize early ADME screening in drug discovery

Pranav Shah, Elias Carvalho Padilha, Rintaro Kato, Vishal B. Siramshetty et autres

Hepatic metabolic stability is a crucial determinant of oral bioavailability and plasma concentrations of a compound, and its measurement is important in early drug discovery. Preliminary metabolic stability estimations are commonly performed in liver microsomal fractions. At the National Center for Advancing …

us (code pays fourni par la source)

Use of physiological based pharmacokinetic modeling for cross-species prediction of pharmacokinetic and tissue distribution profiles of a novel niclosamide prodrug

Mengbi Yang, Amy Q. Wang, Elias Carvalho Padilha, Pranav Shah et autres

Introduction: Niclosamide (Nc) is an FDA-approved anthelmintic drug that was recently identified in a drug repurposing screening to possess antiviral activity against SARS-CoV-2. However, due to the low solubility and permeability of Nc, its in vivo efficacy was limited by its poor …

us (code pays fourni par la source)

Predictive Models for Human Cytochrome P450 3A7 Selective Inhibitors and Substrates

Tuan Xu, Md Kabir, Srilatha Sakamuru, Pranav Shah et autres

Inappropriate use of prescription drugs is potentially more harmful in fetuses/neonates than in adults. Cytochrome P450 (CYP) 3A subfamily undergoes developmental changes in expression, such as a transition from CYP3A7 to CYP3A4 shortly after birth, which provides a potential way to distinguish …

us (code pays fourni par la source)

Development of an improved and specific inhibitor of NADPH oxidase 2 to treat traumatic brain injury

Hannah D. Mason, Ganesha Rai, A. V. Kozyr, Nathaniel De Jonge et autres

NADPH oxidases (NOX's), and the reactive oxygen species (ROS) they produce, play an important role in host defense, thyroid hormone synthesis, apoptosis, gene regulation, angiogenesis and other processes. However, overproduction of ROS by these enzymes is associated with cardiovascular disease, fibrosis, traumatic …

us (code pays fourni par la source)

Pharmacokinetics of isoniazid in Wistar rats exposed to ethanol

Taísa Busaranho Franchin, Jonata Augusto de Oliveira, Caroline Damico Cândido, Evelin dos Santos Martins et autres

Abstract Tuberculosis treatment consists of a drug combination, where isoniazid is the core drug and alcoholism is a factor highly related to poor patient compliance with the therapy. CYP2E1 is an enzyme involved both in the metabolism of ethanol and in the …