Odevixibat (A4250) is a potent and selective inhibitor of intestinal bile acid transporter (IBAT), with an IC50 value of 0.16nM[1]. Odevixibat reduces the reuptake of bile acids from the intestine to the serum and clears bile acids in the colon, thereby lowering the bile acid levels in the serum[2]. Odevixibat has been used to study the regulation of serum bile acids and improvement of liver parameters[3].
In vivo, Odevixibat treatment (10mg/kg/day; p.o.) for 4 weeks significantly ameliorated liver fibrosis, reduced hepatic collagen deposition and α-SMA expression, and improved liver function indicators in Slc27a5−/− mice[4]. In Mdr2−/− mice, dietary treatment with 0.01% (w/w) Odevixibat for 4 weeks significantly mitigated sclerotizing cholangitis, reduced bile duct damage, decreased bile acid secretion, and increased fecal bile acid excretion[5].
References:
[1] Wang Q, Han J, Sorochinsky A, et al. The latest FDA-approved pharmaceuticals containing fragments of tailor-made amino acids and fluorine[J]. Pharmaceuticals, 2022, 15(8): 999.
[2] Al Shaer D, Al Musaimi O, Albericio F, et al. 2021 FDA TIDES (peptides and oligonucleotides) harvest[J]. Pharmaceuticals, 2022, 15(2): 222.
[3] Thompson R J, Artan R, Baumann U, et al. Interim results from an ongoing, open-label, single-arm trial of odevixibat in progressive familial intrahepatic cholestasis[J]. Jhep Reports, 2023, 5(8): 100782.
[4] Wu K, Liu Y, Xia J, et al. Loss of SLC27A5 activates hepatic stellate cells and promotes liver fibrosis via unconjugated cholic acid[J]. Advanced Science, 2024, 11(2): 2304408.
[5] Baghdasaryan A, Fuchs C D, Österreicher C H, et al. Inhibition of intestinal bile acid absorption improves cholestatic liver and bile duct injury in a mouse model of sclerosing cholangitis[J]. Journal of hepatology, 2016, 64(3): 674-681.
Odevixibat（A4250）是一种强效、选择性的肠道胆汁酸转运蛋白（IBAT）抑制剂，IC50值为0.16nM[1]。Odevixibat通过减少肠道对胆汁酸的再吸收并促进结肠清除胆汁酸，从而降低血清胆汁酸水平[2]，Odevixibat已被用于血清胆汁酸调节和改善肝脏功能指标相关研究[3]。
在体内，Slc27a5−/−小鼠口服10mg/kg/day剂量的Odevixibat连续4周后，肝脏纤维化显著改善，表现为肝胶原沉积减少、α-SMA表达下降，同时肝功能指标得到提升[4]。在Mdr2−/−小鼠模型中，饲喂含0.01%（w/w）Odevixibat的饮食4周可明显缓解硬化性胆管炎症状，包括胆管损伤减轻、胆汁酸分泌减少以及粪便胆汁酸排泄增加[5]。