Perfluorooctane Sulfonate-Induced Hepatic Steatosis in Male Sprague Dawley Rats is not Attenuated by Dietary Choline Supplementation
ABSTRACT Perfluorooctane sulfonate (PFOS) is an environmentally persistent chemical. Dietary 100 ppm PFOS fed to male mice and rats for four weeks caused hepatic steatosis through an unknown mechanism. Choline deficient diets can cause hepatic steatosis. A hepatic...
Triazolone Compounds and Uses Thereof: Patent Application
ABSTRACT The invention disclosed herein is directed to compounds of Formula I and pharmaceutically acceptable salts thereof, which are useful in the treatment of prostate, breast, colon, pancreatic, human chronic lymphocytic leukemia, melanoma and other cancers. The...
GPR40 partial agonist MK-2305 lower fasting glucose in the Goto Kakizaki rat via suppression of endogenous glucose production
ABSTRACT GPR40 (FFA1) is a fatty acid receptor whose activation results in potent glucose lowering and insulinotropic effects in vivo. Several reports illustrate that GPR40 agonists exert glucose lowering in diabetic humans. To assess the mechanisms by which GPR40...
In vitro and in vivo pharmacology of NXT629, a novel and selective PPARα antagonist
ABSTRACT Peroxisome-proliferator activated receptors (PPAR) are members of the nuclear hormone receptor superfamily which regulate gene transcription. PPARα is a key regulator of lipid homeostasis and a negative regulator of inflammation. Under conditions of metabolic...
Structure-activity relationship analysis of mitochondrial toxicity caused by antiviral ribonucleoside analogs
ABSTRACT Recent cases of severe toxicity during clinical trials have been associated with antiviral ribonucleoside analogs (e.g. INX-08189 and balapiravir). Some have hypothesized that the active metabolites of toxic ribonucleoside analogs, the triphosphate forms,...
Structural basis for differential activities of enantiomeric PPARγ agonists: Binding of S35 to the alternative site
ABSTRACT Peroxisome proliferator-activated receptor γ (PPARγ) is a member of the nuclear receptor superfamily. It functions as a ligand-activated transcription factor and plays important roles in the regulation of adipocyte differentiation, type 2 diabetes mellitus,...
Novel Small Molecule Guanidine Sigma1 Inhibitors for Advanced Prostate Cancer
ABSTRACT Prostate cancer is the most frequently diagnosed malignancy and the leading cause of cancer related death in men. First line therapy for disseminated disease relies on androgen deprivation, leveraging the addiction of these tumors on androgens for both growth...
Profiling Drug Activity of Human and Ortholog Xenobiotic-Sensing Receptors: PXR, CAR, AhR, and FXR
View Full Size Research conducted by: Koji Toyokawa (1), Ewa Maddox (1), Jack Vanden Huevel (1,2), & Bruce Sherf (1) (1) INDIGO Biosciences, Inc., 1981 Pine Hall Rd, State College, PA, USA (2) Center for Molecular Toxicology and Carcinogenesis, 325 Life Sciences...
Validating the Gene Expression of Clinically Relevant CYP450 Enzymes and Transporters in Human upcyte® Hepatocytes to Develop an In Vitro Predictive Tool for DDI
View Full Size Research conducted by: Samaar Maalouf (1), Bruce Sherf(1), & Jack Vanden Huevel (1,2) (1) INDIGO Biosciences, Inc., 1981 Pine Hall Road, State College, PA, USA (2) Center for Molecular Toxicology and Carcinogenesis, 325 Life Sciences Building, Penn...
Pyrintegrin Induces Soft Tissue Formation by Transplanted or Endogenous Cells
ABSTRACT Focal adipose deficiency, such as lipoatrophy, lumpectomy or facial trauma, is a formidable challenge in reconstructive medicine, and yet scarcely investigated in experimental studies. Here, we report that Pyrintegrin (Ptn), a 2,4-disubstituted pyrimidine...