Incazelo

I-Obeticholic acid (INT-747) iyi-agonist enamandla, ekhethayo futhi esebenza ngomlomo ene-EC50 ye-99 nM.I-Obeticholic acid ine-anticholeretic kanye ne-anti-inflammation effect.I-Obeticholic acid iphinda idale i-autophagy [1][2][3].

Ingemuva

I-Obeticholic Acid (6alpha-ethyl-chenodeoxycholic acid, 6-ECDCA, INT-747) iyi-agonist enamandla futhi ekhethayo ye-FXR enevelu ye-EC50 engu-99 nM [1].

I-farnesoid X receptor (FXR) iyi-nuclear bile acid receptor ebandakanyeka ku-bile acid homeostasis, isibindi fibrosis, ukuvuvukala kwesibindi kanye nesifo senhliziyo [2].

I-Obeticholic Acid iyi-agonist enamandla futhi ekhethayo ye-FXR enomsebenzi we-anticholeretic [1].I-Obeticholic Acid iyi-semisynthetic bile acid derivative kanye ne-FXR ligand enamandla.Emagundaneni e-cholestasis enziwe nge-estrogen, i-6-ECDCA ivikelwe ngokumelene ne-cholestasis eyenziwa yi-17α-ethynylestradiol (E217α) [2].Kumamodeli wamagundane we-cirrhotic portal hypertension (PHT), i-INT-747 (30 mg/kg) iphinde yavuselela indlela yokusayina ye-FXR eyehla nomfula futhi yanciphisa ukucindezela kwe-portal ngokwehlisa inani eliphelele le-intrahepatic vascular resistance (IHVR) ngaphandle kwe-systemic hypotension eyingozi.Lo mphumela uhlotshaniswe nomsebenzi owandisiwe we-eNOS [3].Kumodeli ye-Dahl rat ye-hypertension ezwela usawoti kanye ne-insulin-resistance (IR), ukudla okunosawoti omningi (HS) kwandise kakhulu umfutho wegazi wesistimu kanye nokubonakaliswa kwe-DDAH kwezicubu.I-INT-747 ithuthukise ukuzwela kwe-insulin futhi ivimbele ukwehla kwesisho se-DDAH [4].

Izithenjwa:
[1].Pellicciari R, Fiorucci S, Camaioni E, et al.I-6alpha-ethyl-chenodeoxycholic acid (6-ECDCA), i-FXR enamandla futhi ekhethayo i-agonist enikezwe umsebenzi we-anticholestatic.J Med Chem, 2002, 45(17): 3569-3572.
[2].Fiorucci S, Clerici C, Antonelli E, et al.Imiphumela yokuvikela ye-6-ethyl chenodeoxycholic acid, i-farnesoid X receptor ligand, ku-cholestasis eyenziwe nge-estrogen.J Pharmacol Exp Ther, 2005, 313(2): 604-612.
[3].Verbeke L, Farre R, Trebicka J, et al.I-Obeticholic acid, i-farnesoid X receptor agonist, ithuthukisa i-portal hypertension ngezindlela ezimbili ezihlukene kumagundane acirrhotic.I-Hepatology, 2014, 59(6): 2286-2298.
[4].Ghebremariam YT, Yamada K, Lee JC, et al.I-FXR agonist INT-747 ilawula isisho se-DDAH futhi ithuthukisa ukuzwela kwe-insulin kumagundane e-Dahl anosawoti omningi.I-PLoS One, 2013, 8(4): e60653.

Ukucaphuna Komkhiqizo

• 1. Selina Costa."Ukufanisa i-Novel Ligand ye-Farnesoid X Receptor usebenzisa i-Transgenic Zebrafish."Inyuvesi yaseToronto.Juni-2018.
• 2. Kent, Rebecca."Imithelela ye-Fenofibrate ku-CYP2D6 kanye Nokulawulwa kwe-ANG1 ne-RNASE4 yi-FXR Agonist Obeticholic Acid."indigo.uic.edu.2017.

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