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Inhibitors of the Apical Sodium-Dependent Bile Acid Transporter (ASBT) as Promising Drugs

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Abstract—

Inhibition of the apical sodium-dependent bile acid transporter (ASBT, also known as IBAT, the ileal bile acid transporter, SLC10A2) leads to impairments in the enterohepatic circulation of bile acids and their excretion with fecal masses. This is accompanied by cholesterol utilization for synthesis of new bile acids. ASBT inhibitors are promising drugs for the treatment of such diseases as non-alcoholic fatty liver disease, non-alcoholic steatohepatitis, type 2 diabetes mellitus, necrotic enterocolitis, chronic constipation, and atherosclerosis. To date the most known chemically synthesized inhibitors are: A3309, SHP626, A4250, 264W94, GSK2330672, SC-435. All of them are at different stages of clinical trials, which confirm high efficacy and good tolerance of these inhibitors. Current trends in this field also include directed chemical synthesis of ASBT inhibitors, as well as their search among substances of plant origin.

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  1. Prof. V.F. Voino-Yasenetsky Krasnoyarsk State Medical University, ul. Partizana Zheleznyaka 1, 660022, Krasnoyarsk, Russia

    E. E. Saveleva, E. S. Tyutrina & A. B. Salmina

  2. Faculty of Pharmacy, Takasaki University of Health and Welfare, Gunma, Japan

    T. Nakanishi

  3. School of Pharmaceutical Sciences, Institute of Medical, Pharmaceutical and Health Sciences, Kanazawa University, Ishikawa, Japan

    I. Tamai

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Saveleva, E.E., Tyutrina, E.S., Nakanishi, T. et al. Inhibitors of the Apical Sodium-Dependent Bile Acid Transporter (ASBT) as Promising Drugs. Biochem. Moscow Suppl. Ser. B 15, 16–26 (2021). https://doi.org/10.1134/S1990750821010078

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