Bestatin 氨肽酶YZ剂

58970-76-6  Bestatin 氨肽酶YZ剂  货号A2575化学性质

CAS号	58970-76-6	SDF	Download SDF
别名	Ubenimex,Bestatin
化学名	(2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoic acid
SMILES	CC(C)CC(C(=O)O)NC(=O)C(C(CC1=CC=CC=C1)N)O
分子式	C16H24N2O4	分子量	308.37
溶解性	≥12.34mg/mL in DMSO	储存条件	Store at -20°C
运输条件	SY装：蓝冰运输。 其他可选规格：常温运输或根据您的要求用蓝冰运输。
一般建议	为了使其更好的溶解，请用37℃加热试管并在超声波水浴中震动片刻。不同厂家不同批次产品溶解度各有差异，仅做参考。若实验所需浓度过大至产品溶解极限，请添加助溶剂助溶或自行调整浓度。

生物活性

描述	Bestatin是一种有效的氨肽酶（aminopeptidase）YZ剂，作用于细胞质氨肽酶、氨肽酶N、锌氨肽酶和氨肽酶B，IC50值分别为0.5 nM、5 nM、0.28 μM和1-10 μM。
靶点	cytosol aminopeptidase	aminopeptidase N	zinc aminopeptidase	amino peptidase B
IC50	0.5 nM	5 nM	0.28 μM	1-10 μM

实验操作

细胞实验[1]：
细胞系	K562和K562/ADR细胞
溶解方法	在DMSO中的溶解度≥12.34mg/mL。为了获得更高的浓度，可以将离心管在37℃加热10分钟和/或在超声波浴中震荡一段时间。原液可以在-20℃以下储存几个月。
反应条件	24 h；100 μM
应用	在K562和K562/ADR细胞中，为了确定APN与MDR的相互作用以及其在MDR中可能发挥的作用，用RT-PCR对APN和MDR1的mRNA水平进行检测。与不同浓度的bestatin孵育24小时后，APN mRNA的水平几乎没有变化。然而，K562/ADR细胞比K562细胞具有显著更低的APN mRNA水平。另一方面，在K562和K562/ADR细胞中，高剂量（100 μM）bestatin诱导MDR1分别上调49.4%和18.0%。该结果在mRNA水平确认了bestatin是P-gp的底物。
动物实验[1]：
动物模型	雄性Wistar大鼠
剂量	4 mg/kg，溶解在生理盐水中；口服给药
应用	Bestatin与CsA联合口服给药，与对照组相比，bestatin的血浆浓度显著增加。与CsA联合使用后，bestatin的Cmax（4.8±0.8 μg/ml vs. 2.4±0.6 μg/ml）和AUC（1.06±0.14 mg min/ml vs. 0.55±0.04 mg min/ml）分别增加了1.97和1.92倍。结果表明，CsA可以增加bestatin的肠吸收。
注意事项	请测试所有化合物在室内的溶解度，实际溶解度和理论值可能略有不同。这是由实验系统的误差引起的，属于正常现象。
References: [1] Huo X, Liu Q, Wang C, et al. Enhancement effect of P-gp inhibitors on the intestinal absorption and antiproliferative activity of bestatin[J]. European Journal of Pharmaceutical Sciences, 2013, 50(3): 420-428.

研究更新
1. 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. doi: 10.3109/08923973.2012.719524. Epub 2012 Sep 7. 
Abstract 
Bestatin potentiated the humoral response to SRBC in mice increasing numbers of PFC AND 2-ME-resistant anti-SRBC antibodies and decreasing total anti-SRBC hemagglutinins; while it partially restored cyclophosphamide-induced immunosuppression in a dose-and-schedule-dependent manner.
2. Methotrexate-bestatin interaction: Involvement of P-glycoprotein and organic anion transporters in rats. Int J Pharm. 2014 Feb 13. pii: S0378-5173(14)00102-1. doi: 10.1016/j.ijpharm.2014.02.020. [Epub ahead of print] 
Abstract 
The intravenous co-administration of bestatin and MTX resulted in increased uptake of them in intestines and decreased uptake in kidney and hOAT1- or hOAT3-HEK 293 cells, which indicates that the interaction of these two drugs occurs through co-transport by P-gp in the intestinal mucosa and OATs in kidney.
3. Enhancement effect of P-gp inhibitors on the intestinal absorption and antiproliferative activity of bestatin. Eur J Pharm Sci. 2013 Nov 20;50(3-4):420-8. doi: 10.1016/j.ejps.2013.08.010. Epub 2013 Aug 25. 
Abstract 
Reduced intestinal absorption and accumulation of bestatin was caused by P-gp-mediated efflux and could be restored by the addition of P-gp inhibitors (verapamil or Cyclosporin A) or P-gp substrates (doxorubicin) leading to decreased IC50 value and increased level of bestatin.
4. [Inhibition of tumor cell invasion and induction of apoptosis by ubenimex]. Yao Xue Xue Bao. 2012 Dec;47(12):1593-8. 
Abstract 
Bestatin (Ubenimex) at high concentration inhibited proliferation of tumor cells (HT-1080) and induced apoptosis and cell arrest at G1 phase; while it at low concentration inhibited the aminopeptidase activity and invasion of tumor cells.
5. Organic anion transporters involved in the excretion of bestatin in the kidney. Peptides. 2012 Feb;33(2):265-71. doi: 10.1016/j.peptides.2012.01.007. Epub 2012 Jan 18. 
Abstract 
OAT1 and OAT3 have been found to be involved in the renal excretion of bestatin, since reduced uptake of bestatin in hOAT1-HEK and hOAT3-HEK 293 cells were observed in the presence of OAT substrates including PAH, PCG and JBP485.产品描述

Ubenimex(Bestatin)是一种特异性的氨肽酶B和亮氨酸氨肽酶YZ剂，对氨肽酶A、胰蛋白酶、糜蛋白酶、弹性蛋白酶、木瓜蛋白酶、胃蛋白酶或嗜热菌蛋白酶均没有YZ作用。Bestatin在100 pg/ml时不具有抗细菌和抗真菌活性。Bestatin以300 mg/kg的剂量腹腔注射小鼠时具有低毒性，未引起死亡[1]。

Bestatin是从链霉菌Streptomyces olivoreticuli MD976-C72的培养滤液中分离得到的。Bestatin本身不能被酶水解。与Orthophenanthroline不同，Bestatin对氨肽酶B的YZ活性不能通过加入锌离子而解除。Bestatin有一对相邻的氨基和羟基，使其具有与金属螯合的活性[5-7]。Bestatin及其活性异构体（含有erythro-AHPA或(2S, 3S)-AHPA）均可以显著的YZ氨肽酶的活性[8]。

参考文献：
1.  Umezawa H, Aoyagi T, Suda H, Hamada M, Takeuchi T, Bestatin, an inhibitor of aminopeptidase B, produced by actinomycetes, J Antibiot (Tokyo). 1976 Jan; 29(1):97-9.
2.  Umezawa, H., Aoyagi, T., Suda, H., Hamada, M., And Takeuchi, T. 197615. Antibiotics 29, 97.
3.  Suda, H., Takita, T., Aoyagi, T., And Umezawa, H. (1976) J. Antibiotics 29, 100.
4.  Nakamura, H., Suda, H., Takita, T., Aoyagi, T., Umezawa, H., And Iitaka, Y. (1976) J. Antibiotics 29, 102.
5.  Umezawa, S., Tsuchiya, T., And Tatsuta, K. (1966) Bull. Chem. Sot. Japan 39, 1235. 
6.  Barlow, C. B., And Gijthrie, R. D. (1967) J. Chem. Sot. (C) 1194. 
7.  Bukhari, S. T. K., Guthrie, R. D., Scott, A. I., And Wrixon, A. D. (1970) Tetrahedron 26, 3653.
8. Suda et al. Inhibition of aminopeptidase B and leucine aminopeptidase by bestatin and its stereoisomer, Archives of Biochemistry and Biophysics, 77, 196-200 (1976)

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