400-998-5282
专注多肽 服务科研
400-998-5282
专注多肽 服务科研
Bestatin hydrochloride是氨基肽酶N（APN/CD13）抑制剂，其IC50值为14.9±3.4μM。
编号：451725
CAS号：58970-76-6/65391-42-6
单字母：
| 编号: | 451725 |
| 中文名称: | 盐酸乌苯美司、Ubenimex hydrochloride、Bestatin hydrochloride |
| 英文名: | Ubenimex hydrochloride、Bestatin hydrochloride |
| CAS号: | 58970-76-6，no 65391-42-6，盐酸盐 |
| 三字母: | 3-(r)-amino-2-(s)-hydroxy-4-phenylbutanoyl-(s)-leucine |
| 系统命名法: | (2S)-2-[[(2S,3R)-3-amino-2-hydroxy-4-phenylbutanoyl]amino]-4-methylpentanoic acid;hydrochloride |
| 标签: | Aminopeptidase(氨肽酶) |
| Canonical SMILES: | CC(C)CC(C(=O)O)NC(=O)C(C(CC1=CC=CC=C1)N)O.Cl |
| 实验参考方法（Cell experiment）: | Cell lines：Mammary breast cancer cell lines SKRB3. Preparation Method：SKRB3 were cultured in McCoy’s 5A supplemented with 10% fetal bovine serum at 37°C in a humidified 5% CO2 atmosphere. Cells were cultured until they were 70% confluent in 6‑well plate, then a wound was drawn by a sterile 200μl pipette tip. Subsequently, cells were cultured in fresh serum-free medium with/without 0.25mM Bestatin hydrochloride for 24h. Reaction Conditions：0.25mM; 24h Applications： Bestatin hydrochloride can inhibit the migration and proliferation of breast cancer cells. |
| 实验参考方法（Animal experiment）: | Animal models：male and female Balb/c mice Preparation Method：The mice were immunized intraperitoneally with 0.2ml of 10% SRBC suspension (4×108 cells per mouse). The blood was taken from the jugular vein of cross-bred clinically healthy sheep. The sheep blood was collected in sterile manner into Alsever’s solution containing glucose (2.05%), sodium citrate (0.8%), sodium chloride (0.42%), and citric acid (0.055%) and kept there at 4℃ for at least 3 days. The SRBC suspension was prepared extempore in phosphate-buffered saline (PBS). Bestatin hydrochloride was dissolved in PBS. The agent (doses of 10, 1, and 0.1mg/kg) was injected i.p. to mice, 5 or 10 times at 24h intervals before SRBC immunization. The mice were immunized 24h after the last dose of bestatin. Anti-SRBC hemagglutinin titre was determined on days 4, 7, and 14 after SRBC immunization. The blood samples were taken from retro-ocular arteria of halothane anesthetized mice. The sera were obtained by blood centrifugation and inactivated at 56℃ for 30min. The total and 2-mercaptoethanol-resistant serum agglutination titers were defined by active hemagglutination test carried out on microplates. Dosage form：0.1 or 1 or 10mg/kg; i.p. ; 5 or 10 times at 24h intervals Applications：Bestatin hydrochloride potentiated the humoral response to sheep erythrocytes in mice, resulting in an increased number of plaque-forming cells and 2-mercaptoethanol-resistant anti-SRBC hemagglutinations. |
| 参考文献（References）: | [1] MA Y, YANG X, PAN P, et al. Bestatin attenuates breast cancer stemness by targeting puromycin-sensitive aminopeptidase [J]. Discov Oncol, 2024, 15(1): 197. [2] LIS M, SZCZYPKA M, SUSZKO A, et al. The effects of bestatin on humoral response to sheep erythrocytes in non-treated and cyclophosphamide-immunocompromised mice [J]. Immunopharmacol Immunotoxicol, 2013, 35(1): 133-8. |
| 溶解度: | ≥ 125 mg/mL in DMSO, ≥ 34.2 mg/mL in Water, ≥ 68 mg/mL in EtOH |
盐酸乌苯美司是一种已知的氨基肽酶N（APN/CD13）抑制剂，其IC50值为14.9±3.4μM[1]。盐酸乌苯美司还能抑制氨基肽酶B和LTA4水解酶[2, 3]。研究表明，盐酸乌苯美司可增强抗体依赖性细胞介导的细胞毒性和自然杀伤细胞活性[4]。
Bestatin hydrochloride is known to be an inhibitor of Aminopeptidase N (APN/CD13), which has the IC50 values of 14.9±3.4μM[1]. Bestatin hydrochloride can also inhibits aminopeptidase B and LTA4 hydrolase[2, 3]. Bestatin hydrochloride was shown to enhance antibody-dependent cell mediated cytotoxicity and natural killer cell activity[4].
盐酸乌苯美司（10μM；24小时）显著降低了美氟芬（125或250nM；24小时）在AMOaBTZ细胞中诱导的细胞毒性[5]。盐酸贝他斯汀（0.25mM；24小时）可抑制乳腺癌细胞的迁移和增殖[6]。
Bestatin hydrochloride (10μM; 24h) significantly reduced melflufen (125 or 250nM; 24h) induced cytotoxicity in AMOaBTZ cells[5]. Bestatin hydrochloride (0.25mM; 24h) can inhibit the migration and proliferation of breast cancer cells[6].
盐酸乌苯美司（30mg/kg；腹腔注射；15分钟）可减轻单肺通气模型大鼠的急性肺损伤[7]。盐酸乌苯美司（0.1、1或10mg/kg；腹腔注射；以24小时为间隔，注射5或10次）可增强小鼠对绵羊红细胞（SRBC；腹腔注射）悬液的体液免疫反应，从而增加噬斑形成细胞的数量[8]。
Bestatin hydrochloride (30mg/kg; i.p. ; 15min) alleviated the acute lung injury in one-lung ventilation model rats[7]. Bestatin hydrochloride (0.1 or 1 or 10mg/kg; i.p. ; 5 or 10 times at 24h intervals) potentiated the humoral response to sheep erythrocytes (SRBC; i.p. ) suspension in mice, resulting in an increased number of plaque-forming cells[8].
相关文献:
[1] LUAN Y, MA C, SUI Z, et al. LYP3, a new bestatin derivative for aminopeptidase N inhibition [J]. Med Chem, 2011, 7(1): 32-6.
[2] JIA M R, WEI T, XU W F. The Analgesic Activity of Bestatin as a Potent APN Inhibitor [J]. Front Neurosci, 2010, 4(50.
[3] 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 Lett, 2004, 216(1): 35-42.
[4] SCORNIK O A, BOTBOL V. Bestatin as an experimental tool in mammals [J]. Current drug metabolism, 2001, 2(1): 67-85.
[5] BYRGAZOV K, BESSE A, KRAUS M, et al. Novel Peptide-drug Conjugate Melflufen Efficiently Eradicates Bortezomib-resistant Multiple Myeloma Cells Including Tumor-initiating Myeloma Progenitor Cells [J]. Hemasphere, 2021, 5(7): e602.
[6] MA Y, YANG X, PAN P, et al. Bestatin attenuates breast cancer stemness by targeting puromycin-sensitive aminopeptidase [J]. Discov Oncol, 2024, 15(1): 197.
[7] LUO J, MA Q, TANG H, et al. LTB4 Promotes Acute Lung Injury via Upregulating the PLCepsilon-1/TLR4/NF-kappaB Pathway in One-Lung Ventilation [J]. Dis Markers, 2022, 2022(1839341.
[8] LIS M, SZCZYPKA M, SUSZKO A, et al. The effects of bestatin on humoral response to sheep erythrocytes in non-treated and cyclophosphamide-immunocompromised mice [J]. Immunopharmacol Immunotoxicol, 2013, 35(1): 133-8.
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.
