FX-11 (LDHA Inhibitor FX11)
(Synonyms: LDHA Inhibitor FX11) 目录号 : GC34011
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。
Cas No.:213971-34-7
Sample solution is provided at 25 µL, 10mM.
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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]。
| Cell experiment [1]: | |
|
Cell lines |
PC3 and DU145 (prostate carcinoma) 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 |
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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. |
|
References: [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. |
|
| Cas No. | 213971-34-7 | SDF | |
| 别名 | LDHA Inhibitor FX11 | ||
| Canonical SMILES | O=C(C1=C2C=C(CC3=CC=CC=C3)C(C)=CC2=C(CCC)C(O)=C1O)O | ||
| 分子式 | C22H22O4 | 分子量 | 350.41 |
| 溶解度 | DMSO: 250 mg/mL (713.45 mM) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.8538 mL | 14.269 mL | 28.538 mL |
| 5 mM | 0.5708 mL | 2.8538 mL | 5.7076 mL |
| 10 mM | 0.2854 mL | 1.4269 mL | 2.8538 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
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| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
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Quality Control & SDS
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- Purity: >97.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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