Seladelpar is a potent and selective peroxisome proliferator-activated receptor delta (PPARδ) agonist (EC50=2nM). Seladelpar inhibits bile acid synthesis by activating PPARδ. Seladelpar can be used in research related to primary biliary cholangitis (PBC)[1-4].
In vitro, H69 cholangiocytes were treated with Seladelpar (10nM–10μM) for 22-96 hours. Seladelpar significantly increased the expression of PDK4, ANGPTL4, CPT1A, PLIN2, ACSL1, and ABCA1 in a concentration-dependent manner[5]. Primary mouse hepatocytes and primary human hepatocytes were treated with Seladelpar (0.1–10μM) for 48 hours. Seladelpar significantly reduced the expression of cholesterol 7α-hydroxylase (Cyp7a1/CYP7A1) and induced the expression of fibroblast growth factor 21 (Fgf21/FGF21)[6].
In vivo, Seladelpar (10mg/kg/day) was added to a liquid diet and administered to C57BL/6 mice subjected to ethanol feeding for 4 weeks. Seladelpar significantly reduced ethanol-induced liver injury, lowered plasma ALT and AST levels, alleviated hepatic steatosis and inflammation, and restored bile acid homeostasis and intestinal barrier function[7]. Seladelpar (10mg/kg/day) was orally administered to a non-alcoholic steatohepatitis (NASH) C57BL/6JRj mouse model fed a specific diet for 12 weeks. Seladelpar significantly reduced liver fibrosis[8].
References:
[1] Shukla AK, Misra S. Seladelpar: a comprehensive review of its clinical efficacy and safety in the treatment of primary biliary cholangitis. J Basic Clin Physiol Pharmacol. 2025 Aug 11;36(5):331-337.
[2] Khoury AP, Powell J. Seladelpar for the Treatment of Primary Biliary Cholangitis. Ann Pharmacother. 2025 Oct;59(10):951-958.
[3] Kremer AE, Mayo MJ, Hirschfield GM, et al. Seladelpar treatment reduces IL-31 and pruritus in patients with primary biliary cholangitis. Hepatology. 2024 Jul 1;80(1):27-37.
[4] Hoy SM. Seladelpar: First Approval. Drugs. 2024 Nov;84(11):1487-1495.
[5] Xia Wu, Wen-Yen Chen, Jianguo Song, et al. PPAR-delta activation with seladelpar regulates cholangiocyte inflammation. Journal of Hepatology. 2024 June;6:5-8.
[6] Kouno T, Liu X, Zhao H, et al. Selective PPARδ agonist seladelpar suppresses bile acid synthesis by reducing hepatocyte CYP7A1 via the fibroblast growth factor 21 signaling pathway. J Biol Chem. 2022 Jul;298(7):102056.
[7] Chu H, Jiang L, Gao B, et al. The selective PPAR-delta agonist seladelpar reduces ethanol-induced liver disease by restoring gut barrier function and bile acid homeostasis in mice. Transl Res. 2021 Jan;227:1-14.
[8] Choi YJ, Johnson JD, Lee JJ, et al. Seladelpar combined with complementary therapies improves fibrosis, inflammation, and liver injury in a mouse model of nonalcoholic steatohepatitis. Am J Physiol Gastrointest Liver Physiol. 2024 Feb 1;326(2):G120-G132.