A5026557779- Immunotoxicology and immune responses
- Animal testing and alternatives
- Carcinogens and Genotoxicity Assessment
- Melanoma and MAPK Pathways
- Computational Drug Discovery Methods
- Biosimilars and Bioanalytical Methods
- Effects and risks of endocrine disrupting chemicals
- NF-κB Signaling Pathways
- Cell Adhesion Molecules Research
- Hepatitis B Virus Studies
- HIV Research and Treatment
- PI3K/AKT/mTOR signaling in cancer
- Cytokine Signaling Pathways and Interactions
- HIV/AIDS drug development and treatment
- Eosinophilic Disorders and Syndromes
- Cell Image Analysis Techniques
- Pharmacogenetics and Drug Metabolism
- Odor and Emission Control Technologies
- Marine Biology and Environmental Chemistry
- Colorectal Cancer Treatments and Studies
- Lymphoma Diagnosis and Treatment
- Viral Infectious Diseases and Gene Expression in Insects
- Viral Infections and Immunology Research
- Urticaria and Related Conditions
- Statistical Methods in Clinical Trials
Magnolia Solar (United States)
2024
Gilead Sciences (United States)
2011-2022
La Jolla Pharmaceutical (United States)
2013
Pfizer (United States)
2002-2012
National Cancer Institute
2011
Lawrence Livermore National Laboratory
2011
Corning (United States)
1998-2000
(E)-(S)-4-((S)-2-{3-[(5-methyl-isoxazole-3-carbonyl)-amino]-2-oxo-2H-pyridin-1-yl}-pent-4-ynoylamino)-5-((S)-2-oxo-pyrrolidin-3-yl)-pent-2-enoic acid ethyl ester (Compound 1) is a novel, irreversible inhibitor of human rhinovirus (HRV) 3C protease {inactivation rate constant (Kobs/[I]) 223,000 M-1s-1}. In cell-based assays, Compound 1 was active against all HRV serotypes (35 35), clinical isolates (5 5), and related picornaviruses (8 8) tested with mean 50% effective concentration (EC50)...
Human milk lactoferrin (hmLF) is a glycoprotein with well-known effects on immune function. Helaina Inc. has used glycoengineered yeast, Komatagaella phaffii, to produce recombinant human (Helaina rhLF, Effera™) that structurally similar hmLF intended uses as food ingredient. However, earlier FDA reviews of rhLF were withdrawn due insufficient safety data and unanswered questions the experts raised about immunogenicity/immunotoxicity risks orally ingested rhLF. organized panel leading...
An increasing prevalence of overweight and obesity in people living with HIV has been associated initiation antiretroviral therapy integrase strand transfer inhibitors (INSTIs). off-target inhibition the endogenous ligand binding to human melanocortin 4 receptor (MC4R) suggested as a potential mechanism for clinical body weight gain following dolutegravir, an INSTI. In this study, we interrogated several INSTIs their capacity antagonism or agonism MC4R vitro cell-based assays including at...
An international expert working group representing 37 organisations (pharmaceutical/biotechnology companies, contract research organisations, academic institutions and regulatory bodies) collaborated in a data sharing exercise to evaluate the utility of two species within general toxicology studies. Anonymised on 172 drug candidates (92 small molecules, 46 monoclonal antibodies, 15 recombinant proteins, 13 synthetic peptides 6 antibody-drug conjugates) were submitted by 18 organisations. The...
The ICH S1B carcinogenicity global testing guideline has been recently revised with a novel addendum that describes comprehensive integrated Weight of Evidence (WoE) approach to determine the need for 2-year rat study. In present work, experts from different organizations have joined efforts standardize as much possible procedural framework integration evidence associated S1B(R1) WoE criteria. uses pragmatic consensus procedure hazard assessment facilitate transparent, consistent, and...
An international expert group which includes 30 organisations (pharmaceutical companies, contract research organisations, academic institutions and regulatory bodies) has shared data on the use of recovery animals in assessment pharmaceutical safety for early development. These have been used as an evidence-base to make recommendations inclusion toxicology studies achieve scientific objectives, while reducing animal use. Recovery are development provide information potential a toxic effect...
Developmental and reproductive toxicology (DART) has routinely been a part of safety assessment. Attention is now focused on the effects chemicals developing nervous immune systems. This focus developmental neurotoxicology (DNT) immunotoxicology (DIT) based premise that children differ from adults in some aspects their biology and, thus, may also responses to chemicals. session's objective was discuss issues common DNT DIT as they relate DART protocols, including high dose selection maternal...
A recovery phase--a nondosing period that follows the main dosing phase of a study--is sometimes included in nonclinical toxicity studies, and it is designed to understand whether toxicities observed at end are partially or completely reversible. For biopharmaceuticals with long half-lives, inclusion arms can be helpful understanding effects prolonged exposure assessing antidrug antibodies. This commentary discusses when include groups number given study, animals each group, duration phase....
D5 is a low-molecular-weight cyclic siloxane used for industrial and consumer product applications. The objective of the present study was to evaluate subchronic toxicity following 3-month nose-only inhalation exposure. In addition, animals from both sexes control high dose groups were allowed 4-week recovery period observe reversibility, persistence, or delayed occurrence any potential adverse effects. Male female Fischer 344 rats exposed 6 h/day, 5 days/week 3 months target concentrations...
The nonclinical safety profile of GS-8873, a hepatitis B virus RNA transcript inhibitor was evaluated in rat and monkey 13-week toxicity studies with 8-week recovery phases. Vehicle or GS-8873 dosed orally for 13 weeks at 2, 6, 20, 60 mg/kg/day to Wistar Han rats 0.5, 1.5, 3, 6 cynomolgus monkeys. In vitro vivo screening results from an analog discovered prior informed the toxicology study designs. Neuroelectrophysiology neurobehavioral evaluations were included 4 dosing phases GS-8873. No...
D5is a low-molecular-weight cyclic siloxane used for industrial and consumer product applications. The objective of the present study was to evaluate subchronic toxicity D5following 3-month nose-only inhalation exposure. In addition, animals from both sexes control high dose groups were allowed 4-week recovery period observe reversibility, persistence, or delayed occurrence any potential adverse effects. Male female Fischer 344 rats exposed 6 h/day, 5 days/week 3 months target concentrations...
Octamethylcyclotetrasiloxane (D 4 ) is a low-molecular-weight cyclic siloxane used primarily in the synthesis of silicone polymers. The objective present study was to evaluate subchronic toxicity D following 3-month nose-only inhalation exposure. Male and female Fischer 344 rats (20/sex/group) were exposed 6 h/day, 5 days/week for 3 months vapor concentrations 0, 35, 122, 488, 898 ppm . Also, an additional 10 per sex control high-exposure groups allowed 4-week recovery period observe...
D5 is a low-molecular-weight cyclic siloxane used for industrial and consumer product applications. The objective of the present study was to assess potential toxic immunomodulatory consequences inhalation exposure D5. Male female Fischer 344 rats (25/group) were exposed by whole body 0, 10, 25, 75, or 160 ppm 6 h/day, 7 days/week 28 days. Clinical signs, weights, food consumption recorded. On day following final exposure, 10 rats/group/sex euthanized complete necropsy performed. Following...
D5is a low-molecular-weight cyclic siloxane used for industrial and consumer product applications. The objective of the present study was to assess potential toxic immunomodulatory consequences inhalation exposure D5. Male female Fischer 344 rats (25/group) were exposed by whole body 0, 10, 25, 75, or 160 ppm D56 h/day, 7 days/week 28 days. Clinical signs, weights, food consumption recorded. On day following final exposure, 10 rats/group/sex euthanized complete necropsy performed. Following...
Decamethylcyclopentasiloxane (D5) is a cyclic siloxane with wide range of commercial applications. The present study was designed to investigate the effects D5 on expression and activity selected rat hepatic phase I II metabolizing enzymes. Female Fischer-344 rats were exposed 160 ppm vapors (6 h/day, 7 days/week, for 28 days) by whole-body inhalation. Changes in relative abundance microsomal cytochromes P450 (CYP1A, CYP2B, CYP3A, CYP4A), epoxide hydrolase, UDP-glucuronosyltransferase...
There has been an explosion of technology-enabled scientific insight into the basic biology causes adverse events. This driven, in part, by development various "omics" tools (e.g., genomics, proteomics, and metabolomics) associated bioinformatics platforms. Meanwhile, for decades, changes preclinical testing protocols guidelines have limited. Preclinical safety currently relies heavily on use outdated animal models. Application systems methods to evaluation toxicities oncology treatments can...
The carcinogenic potential of nelfinavir mesylate (nelfinavir) was evaluated in a 2-year oral (gavage) study on Sprague-Dawley rats at dose levels 0 (control), (vehicle control), 100, 300 and 1000 mg/kg per day. At the end treatment, increased incidences thyroid follicular cell hyperplasia neoplasms were observed (males) day (both sexes). There no other treatment-related effects tumors sites. Results from previous studies indicated number liver thyroid, as well metabolic profiles that...
The number of anti-inflammatory and immunomodulatory drugs being developed in the pharmaceutical industry has increased considerably past decade. This increase research development been paralleled by questions from both regulatory agencies on how best to assess decreased host resistance infections or adverse immunostimulation caused agents such as anti-cytokine antibodies (e.g., tumor necrosis factor-α inhibitors), anti-adhesion molecule anti-α-4 integrin inhibitors) immunostimulatory...
Exemestane is an irreversible steroidal inhibitor of cytochrome-P450 aromatase required for estrogen synthesis. The safety the drug in pediatric population, particularly males, has not previously been evaluated. Given increased interest treating children with inhibitors, we undertook a study rats to assess potential exemestane alter reproductive development and function when administered juveniles.Male female were treated at doses anticipated produce exposures approximately 2- 35-fold...