Composition containing SUMO inhibitor and application

Abstract

The invention provides a composition containing an SUMO inhibitor, and belongs to the technical field of medicines. The composition is prepared from an FXR (farnesoid X receptor) agonist and the SUMOinhibitor. According to the composition, in the high-activation state of hepatic stellate cells, the FXR (farnesoid X receptor) agonist does not have the effect of inhibiting the activation of the hepatic stellate cells; after the FXR (farnesoid X receptor) agonist and the SUMO inhibitor are compounded, the activation of the hepatic stellate cells can also be inhibited in the high-activation stateof the hepatic stellate cells; and the hepatic stellate cells of an individual with fibrosis symptoms are in an activated state, using the FXR (farnesoid X receptor) agonist alone cannot generate a good anti-fibrosis effect. The composition of the FXR (farnesoid X receptor) agonist and the SUMO inhibitor has the advantages that the activation of the hepatic stellate cells can be obviously inhibitd, deposition of collagenous fibers can be reduced, and therefore a remarkable anti-fibrosis effect can be achieved.

Description

technical field [0001] The invention relates to the technical field of medicine, in particular to a composition containing a SUMO inhibitor and its application. Background technique [0002] The incidence of liver diseases, especially viral hepatitis, fatty liver disease, liver fibrosis and liver cancer, remains high worldwide. For example, the incidence rate of non-alcoholic fatty liver in ordinary adults in Europe and America is 20-33%, and the incidence rate in obese people is 60-90%; the prevalence rate in ordinary adults in China is about 15% (Fan J G, Farrell G C. Epidemiology of non-alcoholic fatty liver disease in China. Journal of Hepatology, 2009, 50(1):204-10.). Liver fibrosis (Fibrosis) is a pathological state, which refers to the transitional deposition of fibrous connective tissue in the liver. Liver fibrosis is an intermediate link in the further development of chronic liver diseases such as chronic viral hepatitis, metabolic disorders, and chronic alcoholic...

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Problems solved by technology

[0005] The results of some previous animal experiments showed that FXR agonists such as OCA have a significant effect on liver fibrosis, and the mechanism of action is that FXR agonists can inhibit the activation of HSC cells by activating the FXR signaling pathway in HSC cells (Fiorucci S, Antonelli E, Rizzo G, et al. The nuclear receptor SHP mediates inhibition of hepatic stellate cells by FXR and protects against liverfibrosis. Gastroenterology. 2004 Nov; 127(5):1497-512. Fiorucci S1, Rizzo G, Antonelli E, et al. A farnesoid x receptor-small heterodimer partner regulatory cascade modulates tissue metalloproteinase inhibitor-1 and matrixmetalloprotease expression in hepatic stellate cells and promotes resolution of liver fibrosis. J Pharmacol Exp Ther.2005 Aug; 314(2):584-95. However, recent research found that , FXR agonists have no effect on the FXR signaling pathway of activated HSC cells, and have no effect on the activation of HSC cells (Kowdley KV, Luketic V, Chapman R, et al.A randomized trial of obeticholic acid monotherapy in patients with primary biliary cholangitis .Hepatology.2018May; 67(5):1890-1902.); In addition, the results of two recent clinical studies showed that compared with placebo, FXR agonists such as OCA did not significantly improve the liver fibrosis indicators of patients Effects (Nevens F, Andreone P, MazzellaG, et al. A Placebo-Controlled Trial of Obeticholic Acid in Primary Biliary Cholangitis. N Engl J Med. 2016 Aug 18; 375(7): 631-43; Kowdley KV, Luketic V, Chapman R, et al. A randomized trial of obeticholic acid monotherapy patients with primary biliary cholangitis. Hepatology. 2018 May; 67(5):1890-1902.)

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