AbMole小讲堂丨Oligomycin A（寡霉素A）：ATP合成酶抑制剂在肿瘤、抗真菌、代谢领域的研究应用

Oligomycin A寡霉素AAbMoleM1997是一种大环内酯类抗生素也是线粒体ATP合成酶F1Fo ATPase的强效抑制剂。它通过不可逆地结合F1Fo ATP酶的F0亚基阻断ATP合成导致细胞能量代谢崩溃。近年来Oligomycin A在抗肿瘤和抗真菌领域受到广泛关注[1]。Oligomycin A寡霉素ACAS No.579-13-5在 K562慢性髓系白血病的IC50为1.52±0.13 nM并对多药耐药亚系K562/4也表现出抑制活性[2]。Oligomycin A对MCF-7乳腺癌的抑制活性也比较强IC50为1.76 ± 0.24 nM[3, 4]当与糖酵解抑制剂如2-脱氧葡萄糖联用可显著增强抗增殖效果[4]。Oligomycin AMCH 32在小鼠异种移植瘤肝癌中显著抑制SALL4 SNU-398和HCC26.1肿瘤生长且未对小鼠体重造成明显影响[5]。Oligomycin A还常用于研究细胞的线粒体例如Oligomycin A可在1 μM的浓度下抑制成纤维细胞的氧化磷酸化以探究细胞供能与衰老之间的关联[6]。Oligomycin A还可以低剂量0.5 mg/kg保护雄性大鼠免受缺血性急性肾损伤[7]。Oligomycin A1 mg/kg腹腔注射有效抑制了小鼠的ATP合成在上述实验中Oligomycin A溶于5%的乙醇95%的生理盐水[8]。 Oligomycin A对多种植物病原真菌如稻瘟病菌(Pyricularia oryzae)、小麦赤霉病菌(Magnaporthe oryzae Triticum)和镰刀菌(Fusarium spp.)均表现出显著抑制效果其机理涉及菌丝生长、孢子萌发、芽管伸长和孢子形成等环节的抑制[9]。范例详解Mitochondrion. 2024 May;76:101856.AbMole的Oligomycin A寡霉素AAbMoleM1997在MELAS成纤维细胞仅需2小时即可抑制氧化磷酸化关联的ATP产生该实验浓度为1 μM参考文献[1] Nafie, M. S.; Alshams, M. A.; Diab, M. K.; et al. Beyond ATP Synthase Inhibition: Chemical Diversification, Bioactivities, and Therapeutic Potential of Oligomycin A.Chemical biology drug design2025,106(4), e70173.[2] Lysenkova, L. N.; Saveljev, O. Y.; Omelchuk, O. A.; et al. Synthesis, antimicrobial and antiproliferative properties of epi-oligomycin A, the (33S)-diastereomer of oligomycin A.Natural product research2020,34(21), 3073-3081.[3] Omelchuk, O. A.; Malyshev, V. I.; Medvedev, M. G.; et al. Stereochemistries and Biological Properties of Oligomycin A Diels-Alder Adducts.The Journal of organic chemistry2021,86(12), 7975-7986.[4] Scherbakov, A. M.; Sorokin, D. V.; Omelchuk, O. A.; et al. Glucose starvation greatly enhances antiproliferative and antiestrogenic potency of oligomycin A in MCF-7 breast cancer cells.Biochimie2021,186, 51-58.[5] Tan, J. L.; Li, F.; Yeo, J. Z.; et al. New High-Throughput Screening Identifies Compounds That Reduce Viability Specifically in Liver Cancer Cells That Express High Levels of SALL4 by Inhibiting Oxidative Phosphorylation.Gastroenterology2019,157(6), 1615-1629.e1617.[6] Lin, Y. H.; Lin, K. L.; Wang, X. W.; et al. Miro1 improves the exogenous engraftment efficiency and therapeutic potential of mitochondria transfer using Whartons jelly mesenchymal stem cells.Mitochondrion2024,76, 101856.[7] Tanaka, R.; Takayama, J.; Takaoka, M.; et al. Retraction: Oligomycin, an F1FO-ATPase Inhibitor, Protects Against Ischemic Acute Kidney Injury in Male but Not in Female Rats.2013,123(3), 227-234.[8] Brum, E. d. S.; Fialho, M. F. P.; Fischer, S. P. M.; et al. Relevance of mitochondrial dysfunction in the reserpine-induced experimental fibromyalgia model.2020,57(10), 4202-4217.[9] Yamamoto, K.; Futamura, Y.; Uson-Lopez, R. A.; et al. YO-001A, a new antifungal agent produced by Streptomyces sp. YO15-A001.The Journal of antibiotics2019,72(12), 986-990.