| Product Description | Information Lanifibranor (IVA-337) is a moderately potent and well balanced panPPARagonist withEC50 valuesof 1537 nM, 866 nM and 206 nM for hPPARα, hPPARδ and hPPARγ, respectively.
Targets PPARγ ; PPARδ ; PPARα 206 nM(EC50); 866 nM(EC50); 1537 nM(EC50)
In vitro IVA337 acts as a pan‐PPAR agonist with moderate and balanced activity on the three PPAR isoforms. IVA337 50% effective concentration (EC50) levels for the human PPARs (hPPARs) were 1.63E-06\u2009M for PPARα, 8.49E-07\u2009M for PPARδ, and 2.28E-07\u2009M for PPARγ. IVA337 EC50 levels for the rodent PPARs were 3.78E-07\u2009M for PPARα, 1.55E-06\u2009M for PPARδ, and 2.23E-07\u2009M for PPARγ. IVA337 inhibits PDGF-induced proliferation, stiffness-induced activation, and TGF-β1-induced overexpression of fibrotic genes in hHSCs (human primary hepatic stellate cells).
In vivo Following a single oral dose (10 mg/kg in methyl cellulose as vehicle) of IVA-337 in C57Bl6 mice, plasma pharmacokinetic parameters are evaluated. The Cmax, Tmax and AUCinf are 10710 ng/mL, 1 h and 29367 h·(ng/mL), respectively. The anti-diabetic effect of IVA-337 was evaluated in db/db mice, an obese rodent model of type 2 diabetes characterized by severe insulin resistance, hypertriglyceridemia, marked hyperglycemia. Treatment of db/db mouse with IVA-337 for 5 days induces a dose dependent and significant decrease of circulating glucose levels: 40% at 10 mg/kg, and 58% at 30 mg/kg. In the same study abnormal plasma triglycerides levels observed in this disease model were markedly corrected following treatment with IVA-337: 33% at 10 mg/kg, and 45% at 30 mg/kg. IVA-337 has no effect on hematocrit, plasma volume or heart weight. IVA-337 demonstrates excellent anti-hyperglycemic and hypolipidemic efficacy in the db/db mouse model, and a significant anti-fibrotic activity in the mouse CCl4-induced liver fibrosis model. IVA337 normalizes insulin sensitivity while controlling body weight gain, adiposity index, and serum triglyceride increases; it decreased liver steatosis, inflammation, and ballooning.
Cell Research(from reference) Cell lines：human primary hepatic stellate cell (hHSC) Concentrations：3 μM Incubation Time：7 days |
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G2227618