[The inhibitors of the apical sodium-dependent bile acid transporter (ASBT) as promising drugs]

Inhibition of the apical sodium-dependent bile acid transporter (ASBT, also known as IBAT - ileal bile acid transporter, SLC10A2) leads to disruption of 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, 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 the 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.

Ingibirovanie apikal'nogo natriĭ-zavisimogo perenoschika zhelchnykh kislot ASBT (apical sodium-dependent bile acid transporter, izvestnogo takzhe kak IBAT — ileal bile acid transporter, SLC10A2) privodit k narusheniiu énterogepaticheskoĭ tsirkuliatsii zhelchnykh kislot i vyvedeniiu ikh s fekal'nymi massami, v otvet na éto v organizme nachinaet raskhodovat'sia kholesterin dlia sinteza novykh zhelchnykh kislot. Ingibitory ASBT iavliaiutsia perspektivnym lekarstvennymi sredstvami dlia lecheniia takikh zabolevaniĭ, kak nealkogol'naia zhirovaia bolezn' pecheni, nealkogol'nyĭ steatogepatit, sakharnyĭ diabet 2 tipa, nekroticheskiĭ énterokolit, khronicheskiĭ zapor, ateroskleroz. Naibolee izvestnymi na segodniashniĭ den' khimicheski sintezirovannymi ingibitorami iavliaiutsia A3309, SHP626, A4250, 264W94, GSK2330672, SC-435. Vse oni nakhodiatsia na raznykh étapakh klinicheskikh issledovaniĭ, rezul'taty kotorykh podtverzhdaiut vysokuiu éffektivnost' i khoroshuiu perenosimost' ukazannykh ingibitorov. Vedutsia raboty po napravlennomu sintezu novykh éffektivnykh i bezopasnykh ingibitorov ASBT, a takzhe ikh poisku sredi veshchestv rastitel'nogo proiskhozhdeniia.

Keywords: 264W94; A3309; A4250; ASBT; GSK2330672; SHP626.