Lonidamine is an inhibitor of hexokinase, mitochondrial pyruvate carrier (with a Ki of 2.5μM in isolated rat liver mitochondria) and plasma membrane monocarboxylate transporter, and also inhibits mitochondrial complex II [1]. Lonidamine is an anti-tumor drug that can inhibit aerobic glycolysis in cancer cells [2]. Lonidamine can be used in the research of mitochondrial metabolism and inflammation [3].
In vitro, Lonidamine (3, 10, and 30μM; 24h) treatment of IL-4, IL-13, and TNF-α-induced human nasal mucosal epithelial cells significantly and dose-dependently reduced the expression of CXCL1 and PTN, confirming its direct anti-inflammatory and anti-resorptive effects on nasal epithelial cells [4]. Lonidamine (150μM; 45min and 3h) treatment of human melanoma DB-1 cells significantly reduced NADH levels, the Fp redox ratio (Fp/(NADH + Fp)) increased, and mitochondrial redox capacity significantly decreased [5].
In vivo, Lonidamine (100mg/kg; ip) treatment for 2 hours significantly reduced the βNTP level in nude mice with DB-1 human melanoma. At the same time, the NTP levels in DB-1, HCC1806, BT-474, A2780 and LNCaP also decreased respectively [6]. Lonidamine (1, 3, and 10mg/kg/day for 11 days; i.g.) treatment alleviated the symptoms of chronic sinusitis mice, reduced sneezing, cytokine release, inflammatory cell infiltration, and goblet cell hyperplasia. Lonidamine inhibits inflammation by inhibiting the differentiation of inflammatory epithelial cells and neutrophils through Cxcl1-Cxcr2 [4].
References:
[1] Shutkov IA, Okulova YN, Tyurin VY, et al. Ru(III) Complexes with Lonidamine-Modified Ligands. Int J Mol Sci. 2021;22(24):13468.
[2] Nancolas B, et al. The anti-tumour agent lonidamine is a potent inhibitor of the mitochondrial pyruvate carrier and plasma membrane monocarboxylate transporters. Biochem J. 2016 Apr 1;473(7):929-36.
[3] Xueqian Yin, et al. Hexokinase 2 couples glycolysis with the profibrotic actions of TGF-β. Sci Signal. 2019 Dec 17;12(612):eaax4067.
[4] Liu J, Wu L, Wei H, et al. Lonidamine alleviates inflammation and tissue remodeling in a mouse model of eosinophilic chronic sinusitis: A single-cell transcriptomics study[J]. International Immunopharmacology, 2025, 163: 115258.
[5] Xu H N, Feng M, Nath K, et al. Optical redox imaging of lonidamine treatment response of melanoma cells and xenografts[J]. Molecular Imaging and Biology, 2019, 21(3): 426-435.
[6] Nath K, Nelson D S, Heitjan D F, et al. Lonidamine induces intracellular tumor acidification and ATP depletion in breast, prostate and ovarian cancer xenografts and potentiates response to doxorubicin[J]. NMR in Biomedicine, 2015, 28(3): 281-290.
Lonidamine是一种己糖激酶、线粒体丙酮酸载体（在分离的大鼠肝脏线粒体中Ki为2.5μM）和质膜单羧酸转运蛋白抑制剂，同时还抑制线粒体复合物 II [1]。Lonidamine是一种抗肿瘤药物，可抑制癌细胞中的有氧糖酵解 [2]。Lonidamine可用于线粒体代谢和炎症的研究 [3]。
在体外，Lonidamine（3, 10和30μM; 24h）处理IL-4、IL-13和TNF-α诱导的人鼻黏膜上皮细胞，显著且剂量依赖性地降低了CXCL1和PTN的表达，证实了其对鼻上皮细胞的直接抗炎和抗重塑作用 [4]。Lonidamine（150μM; 45min和3h）处理人黑色素瘤DB-1细胞，显著降低了NADH水平，Fp氧化还原比（Fp/（NADH+Fp））增加，线粒体氧化还原能力显著降低 [5]。
在体内，Lonidamine（100mg/kg; ip）治疗2小时显著降低了裸鼠DB-1人黑色素瘤的βNTP水平，同时DB-1、HCC1806、BT-474、A2780和LNCaP的NTP的水平也分别下降 [6]。Lonidamine（1, 3和10mg/kg/day; i.g.）治疗11天缓解了慢性鼻窦炎小鼠的症状，减少了打喷嚏、细胞因子释放、炎症细胞浸润以及杯状细胞增生。Lonidamine通过Cxcl1-Cxcr2抑制炎症上皮细胞和嗜中性粒细胞的分化来抑制炎症 [4]。