Ubenimex

개요Bestatin is an aminopeptidase inhibitor originally isolated from S. olivoreticuli. It inhibits aminopeptidase B (IC50 = 0.05 μg/ml), aminopeptidase N (IC50 = 16.9 μM), leucine aminopeptidase (IC50 = 0.01 μg/ml), and the aminopeptidase activity of leukotriene A4 (LTA4) hydrolase (Kapp = 172 nM). It is selective for these aminopeptidases over aminopeptidase A, trypsin, chymotrypsin, elastase, papain, pepsin, and thermolysin. Bestatin inhibits the production of LTB4 in erythrocytes when used at a concentration of 70 μM. It increases the expression of Akt, inhibits proliferation, migration, and invasion, and induces autophagy and apoptosis in 5637 bladder cancer cells. Bestatin (5 and 15 mg/kg) decreases serum levels of LTB4 and reduces tumor growth in a patient-derived xenograft (PDX) mouse model of colorectal cancer.

용도Ubenimex (also known as bestatin) is a competitive aminopeptidase B inhibitor with an IC50 of 100 mg/ml for K562 cells. Proliferation of all the cell lines except KG1 was inhibited by bestatin. P39/TSU, HL60 and U937 were highly sensitive, with 50% growth inhibitory concentration. It is useful in the treatment of non-lymphocytic leukemia. In other types of cancers ubenimex added to radiotherapy or chemotherapy following surgery significantly inmases survival time through immunopotentiation. It is being studied for use in the treatment of acute myelocytic leukemia.

일반 설명Bestatin was found in the culture broth of Streptomyces olivoreticuli in 1976by Umezawa et al. in the course of screening specific enzyme inhibitors of microbial origin. It shows inhibitory activity against specific exopeptidases, e.g., aminopeptidase B and leucine aminopeptidase. However, it does not act against aminopeptidase A, carboxypeptidases A and B, or endopeptidases. Bestatin acts as a bioresponse modifier and shows antitumor activity via stimulation of immuno response in the host. In combination with cytotoxic anticancer drugs, it is now under clinical evaluation for use in cancer therapy.