sprague-dawley rats

2H-Naphth[2′,1′:4,5]indeno[1,2-d][1,3]dioxole, pregn-4-ene-3,20-dione deriv showed high local anti-inflammatory potency and high lung selectivity when tested on Sprague Dawley rats.

Ensartinib (X-396) is a potent and dual ALK/MET inhibitor with IC50s of <0.4 nM and 0.74 nM, respectively. The ability of Ensartinib (X-396) to inhibit the growth of different cancer cell lines harboring ALK fusions or point mutations is tested. Ensartinib is potent in H3122 lung cancer cells harboring EML4-ALK E13;A20 (IC50: 15nM). Ensartinib is also potent in H2228 lung cancer cells harboring EML4-ALK E6a/b; A20 (IC50: 45 nM). Furthermore, X-376 is potent in SUDHL-1 lymphoma cells harboring NPM-ALK (IC50: 9 nM). X-376 also inhibits SY5Y neuroblastoma cells harboring ALK F1174L, MKN-45 gastric carcinoma cells harboring MET dependent, HepG2 cells and PC-9 lung cancer cell lines harboring EGFR exon 19 del with IC50s of 68 nM, 156 nM, 9.644 μM and 2.989 μM, respectively[1]. The effects of Ensartinib (X-396) in vivo against H3122 xenografts are examined. A pharmacokinetic study reveals that Ensartinib shows substantial bioavailability and moderate half-lives in vivo. Nude mice harboring H3122 xenografts are treated with Ensartinib at 25mg/kg bid. Ensartinib significantly delays the growth of tumors compared to vehicle alone. In the xenograft experiments, Ensartinib appears well-tolerated in vivo. Mouse weight is unaffected by Ensartinib treatment. Drug-treated mice appear healthy and do not display any signs of compound related toxicity. To further assess potential side effects of Ensartinib, additional systemic toxicity and toxico-kinetic studies are performed in Sprague Dawley (SD) rats. Following 10 days of repeated oral administration of Ensartinib at 20, 40, 80 mg/kg in SD rats, all animals survive to study termination. The no significant toxicity (NST) levels are determined to be 80mg/kg for Ensartinib. At NST levels, Ensartinib achieves an AUC of 66 μM×hr and a Cmax of 7.19 μM[1]. [1]. Lovly CM, et al. Insights into ALK-driven cancers revealed through development of novel ALK tyrosine kinaseinhibitors. Cancer Res. 2011 Jul 15;71(14):4920-31.

Niaprazine is a histamine H1-receptor antagonist with marked sedative properties. Niaprazine has antihistamine and antiserotonin activities and can be used for sleep disorder research[1][2]. Niaprazine exhibits a low affinity for the vesicular monoamine transporter and for D2, α2, β, H1 and mAch receptors. Niaprazine, particularly the (+)stereoisomer, has a higher affinity for α1 (Ki = 77 nM) and 5-HT2 (Ki = 25 nM) binding sites, but is poorly recognized by 5-HT1A and 5-HT1B binding sites[2]. Niaprazine (60 mg/kg; i.p.; once) treatment increases rat brain 5-hydroxyindole acetic acid (5-HIAA) concentrations 30 min after treatment, and reduced them at 3-8 hr after treatment. Niaprazine also produces a short-lasting depletion of rat brain noradrenaline (NA) and dopamine (DA)[3]. Animal Model: Male Sprague-Dawley rats (150-200 g)[3] [1]. D Scherman, et al. Molecular pharmacology of niaprazine. Prog Neuropsychopharmacol Biol Psychiatry. 1988;12(6):989-1001. [2]. P G Rossi, et al. Niaprazine in the treatment of autistic disorder. J Child Neurol. 1999 Aug;14(8):547-50. [3]. P E Keane, et al. The effect of niaprazine on the turnover of 5-hydroxytryptamine in the rat brain. Neuropharmacology. 1982 Feb;21(2):163-9.

VPC171 is a novel adenosine A1 receptor positive allosteric modulator (PAM).

Ajugasterone C shows significant inhibitory effect at 100 mg/kg dose on rat paw oedema development due to carrageenan-induced inflammation in Sprague Dawley rats.

Big endothelin-1 (rat 1-39), a 39-residue peptide, induces a diuretic and natriuretic response in conscious Sprague-Dawley rats and elevates blood pressure in mice [1].

Trimethylolpropane caprate has developmental toxicity in Sprague-Dawley rats.

Metyrapone (NSC-25265) is an inhibitor of the enzyme STEROID 11-BETA-MONOOXYGENASE. It is used as a test of the feedback hypothalamic-pituitary mechanism in the diagnosis of CUSHING SYNDROME.

DS-1558 is a potent and orally available GPR40 agonist.DS-1558 was found to have potent glucose lowering effects during an oral glucose tolerance test in ZDF rats. DS-1558 significantly and dose-dependently improved hyperglycemia and increased insulin secretion during the oral glucose tolerance test in Zucker fatty rats, the model of insulin resistance and glucose intolerance. DS-1558 not only increased the glucose-stimulated insulin secretion by GLP-1 but also potentiated the maximum insulinogenic effects of GLP-1 after an intravenous glucose injection in normal Sprague Dawley rats.

Sepimostat dimethanesulfonate (FUT-187), a chemical compound, demonstrates neuroprotective properties by antagonizing NR2B N-methyl-D-aspartate receptors at the NR2B subunit's Ifenprodil-binding site. This compound effectively inhibits Ifenprodil binding, exhibiting a Ki value of 27.7 μM[1].

NHE3-IN-3 (Compound 1) is a potent inhibitor of the isoform 3 of the Na+/H+ exchanger (NHE3). It exhibits pIC50 values of 6.2 and 6.6 against human and rat NHE3, respectively. Furthermore, NHE3-IN-3 showcases exceptional oral bioavailability of 98% in Sprague–Dawley rats [1].

The truncated glucagon-like peptides GLP-1(7-37) is naturally occurring peptide product of the preproglucagon gene that are synthesized primarily in the intestine and acts as incretin that are released from the intestine into the bloodstream in response to food and stimulate insulin secretion. GLP-1(7-37) produced a dose-related enhancement of the glucose-stimulated increase in plasma insulin concentration and an increased rate of glucose infusion in Sprague-Dawley Rats at a dosing rang of 0.5, 5, or 50 pmol/min/kg. Further, infusion of GLP-1(7-37) for 60 mins produced a small transitory increase in plasma insulin concentration in fasted rats and fed rats and a slight transitory decrease in plasma glucose concentration. Moreover, GLP-1(7-37) (5 pmol/min/kg IV) infusion for 6 h in Sprague-Dawley rats produced a sustained increase in plasma insulin concentration relative to levels in rats infused with vehicle[1].

Ziprasidone hydrochloride (CP-88059 hydrochloride) is a united 5-HT (serotonin) and dopamine receptor antagonist which shows potent effects of antipsychotic activity.