FX-11 (LDHA Inhibitor FX11) was found to be a potent, competitive inhibitor of the human LDH-A's NADH binding pocket.
货号:ajcx13116
CAS:213971-34-7
分子式:C22H22O4
分子量：350.41
溶解度:DMSO: 250 mg/mL (713.45 mM)
纯度：98%
存储：Store at -20°C
库存：现货

Background:

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].

参考文献:
[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

Protocol:

Cell experiment [1]:
Cell lines
Preparation Method	PC3 and DU145 cells maintained in log phase growth were plated in 96-well plates and treated with 0.25, 0.5, 1.5, 5, 15, 30, 60, 120, and 240 µmol/L FX-11 for 24 hours.
Reaction Conditions	0.25, 0.5, 1.5, 5, 15, 30, 60, 120, and 240 µmol/L for 24 hours
Applications	After treated with FX-11, the metabolic phenotype of the two cell lines in vitro demonstrated no significant difference in extracellular acidification rate (ECAR), oxygen consumption rate (OCR), pyruvate uptake, and lactate production.
Animal experiment [2]:
Animal models	male SCID mice
Preparation Method	groups of five mice were injected with control 2% (vol/vol) DMSO or 42 µg of FX11
Dosage form	Intraperitoneal injection, 42µg daily, for 10 days
Applications	Daily i.p. injection of 42 µg of FX11 also resulted in a remarkable inhibition of tumor growth.
参考文献: [1]: 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. [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).