| Description: |
Lanifibranor is a pan peroxisome proliferator-activated receptor (PPAR) agonist with EC50s of 1.5, 0.87 and 0.21 μM for human PPARα, PPARσ and PPARγ, respectively. |
| Target: |
PPARγ:206 nM (EC50, Human PPARγ)
PPARδ:866 nM (EC50, Human PPARδ)
PPARα:1537 nM (EC50, Human PPARα) |
| In Vivo: |
Lanifibranor is a pan peroxisome proliferator-activated receptor (PPAR) agonist with EC50s of 1.5, 0.87 and 0.21 μM for human PPARα, PPARσand PPARγ[1]. Skin fibrosis is attenuated by Lanifibranor (IVA337) (p<0.05, vehicle vs Lanifibranor at 30 mg/kg and p<0.001, vehicle vs Lanifibranor at 100 mg/kg). Both low and high doses of Lanifibranor cause a significant decrease of collagenous matrix deposition. Administration of high (100 mg/kg) doses of Lanifibranor results in reduced body weight compare with vehicle controls (p<0.05; Lanifibranor at 100 mg/kg vs vehicle). Results demonstrate that activation of Peroxisome proliferator-activated receptors (PPARs) with Lanifibranor induces a significant reduction in the infiltration of macrophages, CD45+ leucocytes and lymphocytes in Lanifibranor-treated mice compare with rosiglitazone-treated counterparts[2]. |
| Animal Administration: |
Male, aged 6 weeks, C57BL/6 mice are used in different animal trials. (i) Experimental dermal fibrosis (preventative model) is induced with bleomycin (n=6 each group). Concurrent treatment with local injections of bleomycin (0.5 mg/mL) and either Lanifibranor (IVA337) (30 mg/kg), Lanifibranor (100 mg/kg) or vehicle by daily oral gavage continued for 3 weeks. (ii) Experimental dermal fibrosis (curative model) is induced using subcutaneous bleomycin for 6 weeks, but 3 weeks after the first injection, mice are given a daily dose of either Lanifibranor (30 mg/kg), Lanifibranor (100 mg/kg) or vehicle by oral gavage for the remaining 3 weeks[2]. |
| References: |
[1]. Boubia B, et al. Design, Synthesis, and Evaluation of a Novel Series of Indole Sulfonamide Peroxisome Proliferator Activated Receptor (PPAR) α/γ/δ Triple Activators: Discovery of Lanifibranor, a New Antifibrotic Clinical Candidate. J Med Chem. 2018 Feb 27.
[2]. Ruzehaji N, et al. Pan PPAR agonist IVA337 is effective in prevention and treatment of experimental skin fibrosis. Ann Rheum Dis. 2016 Dec;75(12):2175-2183. |
