FX-11 (LDHA Inhibitor FX11) was found to be a potent, competitive inhibitor of the human LDH-A's NADH binding pocket [1]. FX-11 was recharacterized using purified human liver LDHA with Ki of 8μM [2] FX11 inhibition of LDHA increased nonproductive mitochondrial respiration, leading to decreased ATP levels and cell proliferation, and increased oxygen consumption, ROS production and cell death [5].
FX-11 (IC50) for proliferation of DU145 and PC3 (prostate carcinoma) cell lines in vitro was strikingly similar (32 ± 1.1 μmol/L vs. 27 ± 1.1 μmol/L, respectively) [3]. Low concentrations of FX-11 could markedly decrease cell viability in the MPS2(the glycolytic subtype with upregulated carbohydrate and nucleotide metabolism) PDO (Patient-derived organoid) models [4].
FX-11, effectively inhibited tumor growth in human B-lymphoma and pancreatic cancer xenograft models. FX-11 could inhibit tumor growth in P493 lymphomas and human P198 pancreatic tumors ≥200 mm3 [5].
References:
[1]. EC Calvaresi. Small molecule inhibitors of lactate dehydrogenase a as an anticancer strategy. 2014.
[2]: Le, A. et al. Inhibition of lactate dehydrogenase A induces oxidative stress and inhibits tumor progression. Proc. Natl Acad. Sci. USA 107, 2037-2042 (2010).
[3]. Scroggins BT, Matsuo M, White AO, et al. Hyperpolarized [1-13C]-pyruvate magnetic resonance spectroscopic imaging of prostate cancer In Vivo predicts efficacy of targeting the Warburg effect. Clin Cancer Res 2018;24(13):3137-3148.
[4]. Gong Y, Ji P, Yang Y-S, Xie S, Yu T-J, Xiao Y, et al. Metabolic-Pathway-Based Subtyping of Triple-Negative Breast Cancer Reveals Potential Therapeutic Targets. Cell Metab (2021) 33:51-64.e9. doi: 10.1016/j.cmet.2020.10.012
[5]. P. Miao, S. Sheng, X. Sun, J. Liu, G. Huang.Lactate dehydrogenase A in cancer: a promising target for diagnosis and therapy. IUBMB Life, 65 (11) (2013), pp. 904-910
FX-11（LDHA 抑制剂 FX11）被发现是一种有效的竞争性人 LDH-A 的 NADH 结合口袋抑制剂[1]。使用 Ki 为 8μM [2] 的纯化人肝 LDHA 对 FX-11 进行了重新表征。细胞死亡[5].
FX-11 (IC50) 对于 DU145 和 PC3（前列腺癌）细胞系的体外增殖非常相似（分别为 32 ± 1.1 μmol/L 和 27 ± 1.1 μmol/L）[3] 。低浓度的 FX-11 可显着降低 MPS2（碳水化合物和核苷酸代谢上调的糖酵解亚型）PDO（患者来源的类器官）模型中的细胞活力[4]。
FX-11,有效抑制人 B 淋巴瘤和胰腺癌异种移植模型中的肿瘤生长。 FX-11可抑制P493淋巴瘤和人P198胰腺肿瘤≥200 mm3的肿瘤生长[5]。