BAM15（AbMole，M8653）是一种新型合成的线粒体解偶联剂，可破坏电子传递链与ATP合成之间的质子梯度。其作用原理如下：BAM15具有离子载体的特性，可在双层脂膜中诱导质子传导，导致跨线粒体内膜的质子梯度消失，增加活性氧积累，并抑制细胞增殖和迁移[1]。上述效应已在人乳腺癌细胞系MDA-MB-231和小鼠乳腺癌细胞系EO771中得到验证[2]。此外，BAM15（AbMole，M8653）通过抑制线粒体的功能还可调控巨噬细胞极化，在RAW264.7小鼠巨噬细胞中显著抑制促炎性M1型极化，同时促进抗炎性M2型标志基因表达[3]。在动物实验中，C57BL/6J小鼠经BAM15干预后表现出显著的体重控制效果，同时伴随糖代谢改善和肝脏脂肪沉积减少[4]。BAM15的纳米颗粒形式（以PLGA作为载体）在LPS（Lipopolysaccharides，脂多糖） 诱导的脓毒症小鼠模型中显示：该纳米粒子可被脾脏和肝脏巨噬细胞特异性摄取，减轻全身炎症反应并保护肝损伤[3]。BAM15还被用于增强CD7CAR-T细胞的抗肿瘤功能：在异种移植小鼠模型中，低浓度的BAM15即可提升细胞毒性并降低细胞因子释放[5]。
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参考文献及鸣谢
[1] Firsov, A. M.; Popova, L. B.; Khailova, L. S.; et al. Protonophoric action of BAM15 on planar bilayers, liposomes, mitochondria, bacteria and neurons. Bioelectrochemistry (Amsterdam, Netherlands)2021, 137, 107673.
[2] Zunica, E. R. M.; Axelrod, C. L.; Cho, E.; et al. Breast cancer growth and proliferation is suppressed by the mitochondrial targeted furazano[3,4-b]pyrazine BAM15. Cancer & metabolism2021, 9 (1), 36.
[3] Udompornpitak, K.; Bhunyakarnjanarat, T.; Saisorn, W.; et al. Polymeric Particle BAM15 Targeting Macrophages Attenuates the Severity of LPS-Induced Sepsis: A Proof of Concept for Specific Immune Cell-Targeted Therapy. Pharmaceutics2023, 15 (12).
[4] Axelrod, C. L.; King, W. T.; Davuluri, G.; et al. BAM15-mediated mitochondrial uncoupling protects against obesity and improves glycemic control. EMBO molecular medicine2020, 12 (7), e12088.
[5] Ma, Y.; Zhang, H.; Dou, L.; et al. Mitochondrial uncoupler BAM15 enhances the function of CD7CAR-T(CD7-) cells and reduces the release of cytokines for the therapy of T-cell malignancies. International immunopharmacology2025, 155, 114577.
