Bestatin is known to be an inhibitor of Aminopeptidase N (APN/CD13), which has the IC50 values of 14.9±3.4μM[1]. Bestatin can also inhibits aminopeptidase B and LTA4 hydrolase[2, 3]. Bestatin was shown to enhance antibody-dependent cell mediated cytotoxicity and natural killer cell activity[4].
Bestatin (10μM; 24h) significantly reduced melflufen (125 or 250nM; 24h) induced cytotoxicity in AMOaBTZ cells[5]. Bestatin (0.25mM; 24h) can inhibit the migration and proliferation of breast cancer cells[6].
Bestatin (30mg/kg; i.p. ; 15min) alleviated the acute lung injury in one-lung ventilation model rats[7]. Bestatin (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].
References:
[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.
Bestatin是氨基肽酶N（APN/CD13）抑制剂，其IC50值为14.9±3.4μM[1]。Bestatin还能抑制氨基肽酶B和LTA4水解酶[2,3]。Bestatin可增强抗体依赖细胞介导的细胞毒性和自然杀伤细胞活性[4]。
Bestatin（10μM; 24h）显著削弱了melflufen（125 or 250nM; 24h）诱导的AMOaBTZ细胞毒性[5]。Bestatin（0.25mM; 24h）可抑制乳腺癌细胞的迁移和增殖[6]。
使用Bestatin（30mg/kg; i.p. ; 15min）处理单肺通气模型大鼠，Bestatin可减轻大鼠急性肺损伤[7]。使用Bestatin（0.1 or 1 or 10mg/kg; i.p. ; 5 or 10 times at 24h intervals）处理使用SRBC（sheep erythrocytes，绵羊红细胞；i.p.）悬液免疫的小鼠，Bestatin增强了小鼠对SRBC悬液的体液免疫反应，产生更多的空斑形成细胞[8]。