A novel selective NLRP3 inhibitor shows disease-modifying potential in animal models of Parkinson's disease.

Pathological activation of the Nod-like receptor family pyrin domain containing protein 3 (NLRP3) inflammasome signaling underlies many autoimmune and neuroinflammatory conditions. Here we report that, a rationally designed, novel, orally active, selective NLRP3 inflammasome inhibitor, Usnoflast (ZYIL1), showed potent inhibition of ATP, Nigericin and monosodium urate-mediated interleukin (IL)-1β release in THP-1 cells and human PBMC. In isolated microglia cells, the IC of ZYIL1 mediated inhibition of IL-1β was 43 nM.

Safety Assessment of a Novel Intravenous Diclofenac Sodium Formulation Following 28-Day Repeated Administration in Wistar Rats.

These toxicity studies aimed to assess the safety and tolerability of a novel intravenous diclofenac sodium (37.5 mg/mL) formulation containing povidone K12 (80 mg/mL) as the key excipient in Wistar rats. This formulation was tested at doses of 3, 7, and 15 mg/kg/day and was administered daily for 28 days by intravenous route.

Saroglitazar suppresses the hepatocellular carcinoma induced by intraperitoneal injection of diethylnitrosamine in C57BL/6 mice fed on choline deficient, l-amino acid- defined, high-fat diet.

Background: Saroglitazar is a novel PPAR-α/γ agonist with predominant PPAR-α activity. In various preclinical models, saroglitazar has been shown to prevent & reverse symptoms of NASH. In view of these observations, and the fact that NASH is a progressive disease leading to HCC, we hypothesized that saroglitazar may prevent the development of HCC in rodents.

Discovery of a potent G-protein-coupled receptor 119 agonist for the treatment of type 2 diabetes.

The ever-growing prevalence of Type-2 diabetes in the world has an urgent need for multiple orally effective agents that can regulate glucose homeostasis. G-Protein coupled receptor 119 (GPR 119) agonists have demonstrated the glucose-dependent insulin secretion and showed beneficial effects on glycemic control in humans and/or relevant animal models. Herein, we describe our efforts towards identification of a potent and oral GPR 119 agonist 13c (ZY-G19), which showed in vitro potency in the cell-based assay and in vivo efficacy without exerting any significant signs of toxicity in relevant animal models.

Influence of estrous stages on electrocardiography, clinical pathology and ovarian weight of experimental beagle dogs: a retrospective analysis.

Estrous cycle is a repetitive phenomenon occurring during the reproductive life of a female dog. The duration of the canine estrous cycle is considerably longer than one in the most of the other animals and is broadly grouped into follicular phase (proestrus and estrus), luteal phase (diestrus) and non-seasonal anestrus. Dogs in the same stage of cycle can be inadvertently assigned to same group during routine safety and metabolic studies leading to possible erroneous interpretation of test-item related effects.