400-998-5282
专注多肽 服务科研
400-998-5282
专注多肽 服务科研
Bestatin是一种氨基肽酶抑制剂，最初从橄榄网状链霉菌（S. olivoreticuli）中分离得到。
编号：566619
CAS号：223763-80-2
单字母：
| 编号: | 566619 |
| 中文名称: | 乌苯美司三氟乙酸盐、Bestatin trifluoroacetate、Ubenimex trifluoroacetate |
| 英文名: | Bestatin trifluoroacetate、Ubenimex trifluoroacetate |
| CAS号: | 223763-80-2 |
| 三字母: | 223763-80-2 |
| 分子式: | C18H25F3N2O6 |
| 标签: | 现货多肽 Aminopeptidase(氨肽酶) |
| Canonical SMILES: | FC(F)(C(O)=O)F.CC(C)C[C@@H](C(O)=O)NC([C@@H](O)[C@H](N)CC1=CC=CC=C1)=O |
| 实验参考方法（Kinase experiment）: | Cells are harvested, washed, and lysed in NP-40 lysis buffer (50 mM Tris-HCl [pH 7.5], 150 mM NaCl, 0.5% NP-40). Total cell protein is quantified using the Bradford assay and 1-mg/mL protein aliquots are made. Ten microliters of total cell protein is mixed with 290 μL of substrate solution (0.1 mg/mL dithiothreitol [DTT], 0.1 mg/mL albumin, and 1 mM alanine-β-naphthylamide). Fluorometric measurements (340 nm excitation, 400 nm emission) are made after 15 and 30 min. The slope of the line between the 15- and 30-min measurements is used to represent aminopeptidase activity. Total cell protein is preincubated with bestatin, amastatin, puromycin, EDTA, and/or ZnCl2 for 20 min before the fluorometric aminopeptidase assay. |
| 实验参考方法（Cell experiment）: | Growing cells (1×106 to 2×106 cells/mL) are diluted to 1.0×103 cells/mL and transferred (3 mL) into a well in a 12-well multiwell plate (2.5-cm diameter/well). Cells are treated with 0, 10, 50, 100, 300, or 600 μM Bestatin and allowed to grow at 21°C shaking at 180 rpm for 48 h. A hemocytometer is used to measure cell density after 0, 24, and 48 h. |
| 实验参考方法（Animal experiment）: | Bestatin is dissolved in PBS. The agent (doses of 10, 1, and 0.1 mg/kg) is injected i.p. to non-cyclophosphamide-treated mice, 5 or 10 times at 24-h intervals before SRBC immunization. The mice are immunized 24 h after the last dose of bestatin. Pharmacological immunosuppression is induced by a single intraperitoneal injection of cyclophosphamide administered at a dose of 350 mg/kg, 12 days before SRBC immunization. Bestatin at the doses of 1 and 0.1 mg/kg is injected to cyclophosphamide-immunosuppressed mice i.p. five times at 48-h intervals or 10 times at 24-h intervals before SRBC immunization. The first dose of bestatin is administered 24 h after cyclophosphamide, while the last dose of the drug is injected 24h before SRBC immunization. |
| 参考文献（References）: | [1]. Hossain A, et al. Protective effects of bestatin in the retina of streptozotocin-induced diabetic mice. Exp Eye Res. 2016 Aug;149:100-6 [2]. Qian X, et al. Inhibition of p38 MAPK Phosphorylation Is Critical for Bestatin to Enhance ATRA-Induced Cell Differentiation in Acute Promyelocytic Leukemia NB4 Cells. Am J Ther. 2016 May-Jun;23(3):e680-9. [3]. Lis M, et al. The effects of bestatin on humoral response to sheep erythrocytes in non-treated and cyclophosphamide-immunocompromised mice. Immunopharmacol Immunotoxicol. 2013 Feb;35(1):133-8 [4]. Poloz Y, et al. Bestatin inhibits cell growth, cell division, and spore cell differentiation in Dictyostelium discoideum. Eukaryot Cell. 2012 Apr;11(4):545-57 |
Bestatin是一种氨基肽酶抑制剂，最初从橄榄网状链霉菌（S. olivoreticuli）中分离得到[1]。它能够抑制氨基肽酶B（IC50=0.05微克/毫升）、氨基肽酶N（IC50=16.9微摩尔）、亮氨酸氨基肽酶（IC50=0.01微克/毫升）以及白三烯A4（LTA4）水解酶的氨基肽酶活性（Kapp=172纳摩尔）[1,2,3]。与氨基肽酶A、胰蛋白酶、胰凝乳蛋白酶、弹性蛋白酶、木瓜蛋白酶、胃蛋白酶和嗜热菌蛋白酶相比，Bestatin对这些氨基肽酶具有更高的选择性[1]。当Bestatin的浓度为70微摩尔时，可抑制红细胞中LTB4的产生[3]。它可增加Akt的表达，抑制5637膀胱癌细胞的增殖、迁移和侵袭，并诱导其自噬和凋亡[4]。在结直肠癌患者来源异种移植（PDX）小鼠模型中，Bestatin（5和15毫克/千克）可降低血清中LTB4的水平并抑制肿瘤生长[5]。
Bestatin is an aminopeptidase inhibitor originally isolated from S. olivoreticuli.1 It inhibits aminopeptidase B (IC50 = 0.05 ?g/ml), aminopeptidase N (IC50 = 16.9 ?M), leucine aminopeptidase (IC50 = 0.01 ?g/ml), and the aminopeptidase activity of leukotriene A4 (LTA4) hydrolase (Kapp = 172 nM).1,2,3 It is selective for these aminopeptidases over aminopeptidase A, trypsin, chymotrypsin, elastase, papain, pepsin, and thermolysin.1 Bestatin inhibits the production of LTB4 in erythrocytes when used at a concentration of 70 ?M.3 It increases the expression of Akt, inhibits proliferation, migration, and invasion, and induces autophagy and apoptosis in 5637 bladder cancer cells.4 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.5
参考文献：
1.Umezawa, H., Ayoagi, T., Suda, H., et al.Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetesJ. Antibiot. (Tokyo)29(1)97-99(1976)
2.Melzig, M.F., and Bormann, H.Betulinic acid inhibits aminopeptidase N activityPlanta Med.64(7)655-657(1998)
3.?rning, L., Krivi, G., and Fitzpatrick, F.A.Leukotriene A4 hydrolase. Inhibition by bestatin and intrinsic aminopeptidase activity establish its functional resemblance to metallohydrolase enzymesJ. Biol. Chem.266(3)1375-1378(1991)
4.Wang, X., Liu, Y., Liu, W., et al.Ubenimex, an APN inhibitor, could serve as an anti?tumor drug in RT112 and 5637 cells by operating in an Akt?associated mannerMol. Med. Rep.17(3)4531-4539(2018)
5.Zhao, S., Yao, K., Li, D., et al.Inhibition of LTA4H by bestatin in human and mouse colorectal cancerEBioMedicine44361-374(2019)
氨基肽酶是一类广泛分布于细菌、真菌、动物和植物中的酶，它们通过水解多肽链N端附近的肽键，催化蛋白质或肽底物氨基末端的氨基酸裂解。大多数氨基肽酶由相对大分子量（50kDa）的亚基组装而成，呈现多聚体结构，而有些则是单聚体。大多数氨基肽酶是锌金属酶，因此会被过渡态类似物bestatin抑制。氨基肽酶存在于许多亚细胞器以及细胞质和膜中，它们参与多种蛋白水解途径，并在蛋白质成熟、非激素和激素肽的降解以及可能决定蛋白质稳定性方面发挥重要作用。
Aminopeptidases are a group of enzymes widely distributed among bacteria, fungi, animals and plants that catalyze the cleavage of amino acids from the amino terminus of protein or peptide substrates through hydrolysis of peptide bonds near the N-terminal end of a polypeptide chain. Most aminopeptidases are assembled by relatively high mass (50kDa) subunits exhibiting multimeric structures, whereas some are monomeric. The majority of aminopeptidases are zinc metalloenzymes and hence inhibited by the transition-state analog bestatin. Aminopeptidases have been found in many subcellular organelles as well as in cytoplasm and membrane, where they are involved in diverse proteolytic pathways and play an essential role in protein maturation, degradation of non-hormonal and hormonal peptides and possibly determination of protein stability.
