An aminopeptidase inhibitor
Bestatin hydrochloride, also known as Ubenimex, is an inhibitor of aminopeptidase B and N (APN)/CD13 [1].
Bestatin, an antibiotic of microbial origin, is a potent inhibitor of some aminopeptidases which can be administered to cultured cells, intact animals and humans with low toxicity. It has been used as an useful tool to assess the physiological role of certain mammalian exopeptidases in the regulation of the immune system, the growth of tumors and their invasion of surrounding tissues, and the degradation of cellular proteins [2].
In vivo: In a mouse dorsal air sac assay, oral administration of bestatin (100-200 mg/kg/day) showed a significant inhibitory activity against the melanoma cell-induced angiogenesis. Bestatin also inhibited the tube-like formation of human umbilical vein endothelial cells (HUVECs). Furthermore, after the orthotopic implantation of B16-BL6 melanoma cells into mice, bestatin administration (50-100 mg/kg/day, i.p) reduced the number of vessels oriented towards the established primary tumor mass on the dorsal side of mice [1].
参考文献:
[1].? Aozuka Y1, Koizumi K, Saitoh Y, Ueda Y, Sakurai H, Saiki I. Anti-tumor angiogenesis effect of aminopeptidase inhibitor bestatin against B16-BL6 melanoma cells orthotopically implanted into syngeneic mice. Cancer Lett. 2004 Dec 8;216(1):35-42.
[2].? Scornik OA1,Botbol V.Bestatin as an experimental tool in mammals. Curr Drug Metab.2001 Mar;2(1):67-85.
| Cell experiment [1]: | |
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Cell lines |
D. discoideum cells, human umbilical vein endothelial cells |
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Preparation method |
Soluble in DMSO. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while. Stock solution can be stored below -20℃ for several months. |
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Reacting condition |
600 μM, 48 h |
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Applications |
Bestatin (600 μM)-treated cells progressed slower through the cell cycle due to decreased rate of cell growth and the frequency of cell division. Bestatin inhibited the frequency of mitosis and the inherent multinuclearity in D. discoideum cells, and was not cytotoxic to D. discoideum cells at 0-600 μM. Bestatin inhibited aminopeptidase activity in lysates of PsaA-GFP- and GFP-expressing cells by 69.39% ± 10.5% and 39.93% ± 18.7% of control, respectively. Bestatin (1-100 μg/ml) dose-dependently inhibited the Ala-MCA-hydrolysing activity of HUVECs. Bestatin inhibited the tube-like formation of HUVECs. |
| Animal experiment [2]: | |
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Animal models |
Inbred 6-week-old female C57BL/6 mice bearing B16-BL6 melanoma xenografts |
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Dosage form |
Oral administration, 100-200 mg/kg/day; Intraperitoneal injection, 50-100 mg/kg/day |
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Application |
In a mouse dorsal air sac assay, oral administration of bestatin (100-200 mg/kg/day) significantly inhibited melanoma cell-induced angiogenesis. After the orthotopic implantation of B16-BL6 melanoma cells into mice, bestatin administration (50-100 mg/kg/day, i.p.) reduced the number of vessels oriented towards the established primary tumor mass on the dorsal side of mice. |
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Other notes |
Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal. |
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参考文献: [1]. Poloz Y, Catalano A, O'Day D H. Bestatin inhibits cell growth, cell division, and spore cell differentiation in Dictyostelium discoideum[J]. Eukaryotic cell, 2012, 11(4): 545-557. [2]. Aozuka Y, Koizumi K, Saitoh Y, et al. Anti-tumor angiogenesis effect of aminopeptidase inhibitor bestatin against B16-BL6 melanoma cells orthotopically implanted into syngeneic mice[J]. Cancer letters, 2004, 216(1): 35-42. |
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