Oligomycin A（寡霉素A，AbMole，M1997）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A，CAS 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 A（MCH 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 A（1 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A，AbMole，M1997）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

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[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 research 2020, 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 chemistry 2021, 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. Biochimie 2021, 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. Gastroenterology 2019, 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 Wharton's jelly mesenchymal stem cells. Mitochondrion 2024, 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 antibiotics 2019, 72 (12), 986-990.