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ʻO ka waika Obeticholic (INT-747) he mea ikaika, koho a hoʻoikaika waha FXR agonist me kahi EC50 o 99 nM. Loaʻa i ka Obeticholic acid ka hopena anticholeretic a me ka anti-inflammation. Hoʻokomo pū ka Obeticholic acid i ka autophagy [1][2][3].

Kāpae

Obeticholic Acid (6alpha-ethyl-chenodeoxycholic acid, 6-ECDCA, INT-747) he agonist ikaika a koho o FXR me ka waiwai EC50 o 99 nM [1].

ʻO ka farnesoid X receptor (FXR) he nuklear bile acid receptor i komo i ka homeostasis acid bile, fibrosis ate, hepatic and intestinal inflammation a me ka maʻi cardiovascular [2].

ʻO ka Obeticholic Acid kahi agonist FXR ikaika a koho me ka hana anticholeretic [1]. ʻO ka Obeticholic Acid he semisynthetic bile acid derivative a me ka ikaika FXR ligand. I ka estrogen-induced cholestasis iole, 6-ECDCA pale aku i ka cholestasis i hookomoia e 17α-ethynylestradiol (E217α) [2]. Ma nā ʻano ʻiole cirrhotic portal hypertension (PHT), ua hoʻāla hou ʻo INT-747 (30 mg/kg) i ke ala hōʻailona FXR downstream a hoʻemi i ke kaomi puka ma ka hoʻohaʻahaʻa ʻana i ka nui o ka intrahepatic vascular resistance (IHVR) me ka ʻole o ka hypotension systemic deleterious. Ua pili kēia hopena me ka hoʻonui ʻana i ka hana eNOS [3]. I ka Dahl rat model o ka paʻakai paʻakai kiʻekiʻe a me ka insulin-kū'ē (IR), kiʻekiʻe paʻakai (HS) meaʻai nui hoʻonui systemic koko a me downregulated kiko DDAH hōʻike. Hoʻonui ka INT-747 i ka naʻau o ka insulin a kāohi i ka emi ʻana o ka ʻōlelo DDAH [4].

Kuhikuhi:
[1]. Pellicciari R, Fiorucci S, Camaioni E, et al. ʻO ka 6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), kahi agonist FXR ikaika a koho i hāʻawi ʻia me ka hana anticholestatic. J Med Chem, 2002, 45(17): 3569-3572.
[2]. Fiorucci S, Clerici C, Antonelli E, et al. Nā hopena pale o 6-ethyl chenodeoxycholic acid, kahi ligand loaʻa X farnesoid, i loko o ka estrogen-induced cholestasis. J Pharmacol Exp Ther, 2005, 313 (2): 604-612.
[3]. Verbeke L, Farre R, Trebicka J, a me al. Obeticholic acid, he farnesoid X receptor agonist, hoʻomaikaʻi i ka hypertension portal ma nā ala ʻelua ʻokoʻa i nā ʻiole cirrhotic. Hepatology, 2014, 59 (6): 2286-2298.
[4]. Ghebremariam YT, Yamada K, Lee JC, et al. Hoʻopili ka FXR agonist INT-747 i ka hōʻike DDAH a hoʻonui i ka ʻike insulin i nā ʻiole Dahl hānai kiʻekiʻe. PLoS One, 2013, 8(4): e60653.

Huahana Huahana

• 1. Selina Costa. "Ke hōʻike ʻana i kahi Novel Ligand no ka Farnesoid X Receptor me ka hoʻohana ʻana i Transgenic Zebrafish." Kulanui o Toronto. Iune-2018.
• 2. Kent, Rebeka. "Nā hopena o Fenofibrate ma CYP2D6 a me ka hoʻoponopono o ANG1 a me RNASE4 e ka FXR Agonist Obeticholic Acid." indigo.uic.edu.2017.

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