Syrosingopine
(Synonyms: 乙酯利血平,Su 3118) 目录号 : GC39536
Syrosingopine是一种双重MCT1/MCT4抑制剂，对MCT1和MCT4的IC50值分别为2.5µM和0.04µM。
Cas No.:84-36-6
Sample solution is provided at 25 µL, 10mM.
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Syrosingopine is a dual MCT1 and MCT4 inhibitor, with IC50 values of 2.5µM and 0.04µM, respectively[1]. Syrosingopine enhances the 20S proteasome and promotes the degradation of fluorogenic substrates and α-synuclein[2]. Syrosingopine has been widely used in cancer cell models to inhibit cell proliferation and to develop novel combination therapies to inhibit tumor growth[3].
In vitro, Syrosingopine treatment for 4 days effectively suppressed the viability of HL60 cells, with an IC50 value of 10µM [4]. Treatment with 10µM Syrosingopine for 72 hours resulted in a significant decrease in glucose consumption and lactate secretion and induced apoptosis in MDA-MB-231 cells[5]. Treatment of leukemic cells with 10µM Syrosingopine for 48 hours inhibited glycolysis, resulting in increased intracellular lactate levels and induced autophagy[6].
In vivo, Syrosingopine treatment via intraperitoneal injection at a dose of 7.5mg/kg every other day for 5 weeks reduced the body weight of mice with liver fibrosis and increased collagen deposition in liver tissues[7]. The combination of Syrosingopine (7.5mg/kg/day) and UK-5099 (3mg/kg/day) administered intraperitoneally for 14 consecutive days significantly inhibited tumor growth in a PC-9 cell xenograft tumor mouse model[8].
References:
[1] Benjamin D, Robay D, Hindupur S K, et al. Dual inhibition of the lactate transporters MCT1 and MCT4 is synthetic lethal with metformin due to NAD+ depletion in cancer cells[J]. Cell reports, 2018, 25(11): 3047-3058. e4.
[2] Sadahiro Y, Nishimura S, Hitora Y, et al. Syrosingopine enhances 20S proteasome activity and degradation of α-synuclein[J]. Journal of Natural Products, 2023, 87(3): 554-559.
[3] Benjamin D, Colombi M, Hindupur S K, et al. Syrosingopine sensitizes cancer cells to killing by metformin[J]. Science advances, 2016, 2(12): e1601756.
[4] Benjamin D, Hall M N. Combining metformin with lactate transport inhibitors as a treatment modality for cancer-recommendation proposal[J]. Frontiers in Oncology, 2022, 12: 1034397.
[5] Buyse C, Joudiou N, Warscotte A, et al. Evaluation of syrosingopine, an MCT inhibitor, as potential modulator of tumor metabolism and extracellular acidification[J]. Metabolites, 2022, 12(6): 557.
[6] Saulle E, Spinello I, Quaranta M T, et al. Targeting lactate metabolism by inhibiting MCT1 or MCT4 impairs leukemic cell proliferation, induces two different related death-pathways and increases chemotherapeutic sensitivity of acute myeloid leukemia cells[J]. Frontiers in oncology, 2021, 10: 621458.
[7] Guo M, Gou Y, Dong X, et al. Syrosingopine, an anti-hypertensive drug and lactate transporter (MCT1/4) inhibitor, activates hepatic stellate cells and exacerbates liver fibrosis in a mouse model[J]. Genes & Diseases, 2024, 11(4): 101169.
[8] Li Y, Song Y, Shi Z, et al. Syrosingopine and UK5099 synergistically suppress non-small cell lung cancer by activating the integrated stress response[J]. Cell Death & Disease, 2024, 15(6): 431.
Syrosingopine是一种双重MCT1/MCT4抑制剂，对MCT1和MCT4的IC50值分别为2.5µM和0.04µM[1]。Syrosingopine能增强20S蛋白酶体活性，促进荧光底物及α-突触核蛋白的降解[2]。Syrosingopine已广泛应用于癌细胞模型中抑制细胞增殖，并用于开发抑制肿瘤生长的新型联合疗法[3]。
在体外，Syrosingopine处理4天可有效抑制HL60细胞活力，IC50值为10µM[4]。使用10µM的Syrosingopine处理MDA-MB-231细胞72小时，能显著降低葡萄糖消耗和乳酸分泌，并诱导细胞凋亡[5]。用10µM的Syrosingopine处理白血病细胞48小时，可抑制糖酵解过程导致细胞内乳酸积累，并诱导自噬发生[6]。
在体内，隔天腹腔注射7.5mg/k剂量的Syrosingopine持续5周，可减轻肝纤维化小鼠的体重，并增加肝组织中的胶原沉积[7]。连续14天每日联合腹腔注射Syrosingopine（7.5mg/kg/day）与UK-5099（3mg/kg/day），能显著抑制PC-9细胞移植瘤小鼠模型的肿瘤生长[8]。
| Cell experiment [1]: | |
Cell lines | PC-9 cells |
Preparation Method | PC-9 cells were cultured in RPMI 1640 medium supplemented with 10% fetal bovine serum and 1% penicillin/streptomycin solution in a constant temperature incubator under a humidified environment of 5% CO2 at 37℃. PC-9 cells were seeded in 96-well plates and treated with various concentrations of Syrosingopine (0, 1, 5, 10, and 20μM) for 48 hours. Subsequently, CCK-8 reagent was added, and absorbance values were measured at a wavelength of 450nm. |
Reaction Conditions | 0, 1, 5, 10, and 20μM; 48h |
Applications | Syrosingopine treatment significantly inhibited the viability of PC-9 cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Male C57BL/6J mice |
Preparation Method | C57BL/6J mice (male, 5-week-old) were randomly divided into 2 groups, with 5 mice in each group, and were intraperitoneally injected with 2.0μl/g of 20% CCl4 solution (in olive oil) twice a week. For the Syrosingopine-treated liver fibrosis group (Fib+Syro), mice were intraperitoneally injected with 7.5mg/kg of Syrosingopine every other day for 5 weeks. Equal volume of DMSO was used at the same frequency to treat the liver fibrosis group (Fib). The dynamic body weight of mice was recorded every week. Mouse liver tissues were removed for analysis. |
Dosage form | 7.5mg/kg; every other day for 5 weeks; i.p. |
Applications | Syrosingopine treatment reduced the body weight of mice and increased collagen deposition in liver tissues. |
References: | |
| Cas No. | 84-36-6 | SDF | |
| 别名 | 乙酯利血平,Su 3118 | ||
| Canonical SMILES | [H][C@@]12C(NC3=C4C=CC(OC)=C3)=C4CCN1C[C@]5(C[C@@H](OC(C6=CC(OC)=C(OC(OCC)=O)C(OC)=C6)=O)[C@H](OC)[C@@H](C(OC)=O)[C@]5(C2)[H])[H] | ||
| 分子式 | C35H42N2O11 | 分子量 | 666.71 |
| 溶解度 | DMSO: 62.5 mg/mL (93.74 mM) | 储存条件 | Store at -20°C, protect from light |
| 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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| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.4999 mL | 7.4995 mL | 14.999 mL |
| 5 mM | 300 μL | 1.4999 mL | 2.9998 mL |
| 10 mM | 150 μL | 750 μL | 1.4999 mL |
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| 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，
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1. 首先保证母液是澄清的；
2.
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