SR 18292
目录号 : GC18269
SR 18292是一种过氧化物酶体增殖物激活受体γ（PPARγ）共激活因子-1α（PGC-1α）的抑制剂，可促进PGC-1α乙酰化，抑制糖异生基因的表达，并减少肝细胞中葡萄糖的产生。
Cas No.:2095432-55-4
Sample solution is provided at 25 µL, 10mM.
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SR 18292 is an inhibitor of peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α), which promotes PGC-1α acetylation, inhibits the expression of gluconeogenic genes, and reduces glucose production in hepatocytes [1]. SR 18292 enhances the interaction between histone acetyltransferase (GCN5) and PGC-1α, subsequently leading to increased PGC-1α acetylation [2]. SR 18292 reduces mitochondrial function and the expression of mitochondrial biogenesis parameters (PGC-1α, NRF2, Tfam) [3].
In vitro, SR 18292 (12.5-200μM) treatment of melanoma A375 and WM115 adherent cells for 48h dose-dependently reduced cell viability, colony formation and migration, and inhibited melanoma cell sphere formation ability and ABCG2 enrichment[4]. SR 18292 (10, 20 μM) treatment of human bone marrow-derived mesenchymal stem cells (hMSC) significantly inhibited the protein level of PGC-1α and increased the protein level of GLUT1, and increased the glucose uptake rate and lactate production rate of hMSC[5]. SR 18292 (20 μM) treatment of NK cells for 48 h or 10 days reversed the increase in cellular IFNγ, mitochondrial mass, membrane potential and glucose uptake induced by docosahexaenoic acid (DHA)[6].
In vivo, SR 18292 (10 mg/kg/day) was treated by intraperitoneal injection in sickle cell disease (SCD) mice for 4 weeks, which significantly reduced the number of irreversibly sickled erythrocytes and reticulocytes in the peripheral blood of mice and improved erythrocyte survival[7]. SR 18292 (30 μg) was treated by intrathecal injection in rats with neuropathic pain (PINP) model, and partially eliminated the analgesic effect of formoterol on PINP[8].
References:
[1] Sharabi K, Lin H, Tavares C D J, et al. Selective chemical inhibition of PGC-1α gluconeogenic activity ameliorates type 2 diabetes[J]. Cell, 2017, 169(1): 148-160. e15.
[2] Yang Y N, Zhang M Q, Yu F L, et al. Peroxisom proliferator-activated receptor-γ coactivator-1α in neurodegenerative disorders: A promising therapeutic target[J]. Biochemical Pharmacology, 2023: 115717.
[3] Xie K, Wang Y, Yin L, et al. Hydrogen gas alleviates sepsis-induced brain injury by improving mitochondrial biogenesis through the activation of PGC-α in mice[J]. Shock, 2021, 55(1): 100-109.
[4] Fontana F, Macchi C, Anselmi M, et al. PGC1-α-driven mitochondrial biogenesis contributes to a cancer stem cell phenotype in melanoma[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2024, 1870(1): 166897.
[5] Jiang B, Huang L, Tian T, et al. IRX5 promotes adipogenesis of hMSCs by repressing glycolysis[J]. Cell Death Discovery, 2022, 8(1): 204.
[6] Wu S, Peng H, Li S, et al. The ω-3 polyunsaturated fatty acid docosahexaenoic acid enhances NK-cell antitumor effector functions[J]. Cancer Immunology Research, 2024, 12(6): 744-758.
[7] Sun Y, Benmhammed H, Al Abdullatif S, et al. PGC-1α agonism induces fetal hemoglobin and exerts antisickling effects in sickle cell disease[J]. Science Advances, 2024, 10(31): eadn8750.
[8] Chen N, Ge M M, Li D Y, et al. β2-adrenoreceptor agonist ameliorates mechanical allodynia in paclitaxel-induced neuropathic pain via induction of mitochondrial biogenesis[J]. Biomedicine & pharmacotherapy, 2021, 144: 112331.
SR 18292是一种过氧化物酶体增殖物激活受体γ（PPARγ）共激活因子-1α（PGC-1α）的抑制剂，可促进PGC-1α乙酰化，抑制糖异生基因的表达，并减少肝细胞中葡萄糖的产生[1]。SR 18292可增强组蛋白乙酰转移酶（GCN5）和PGC-1α之间的相互作用，随后导致PGC-1α乙酰化增加[2]。SR 18292可降低线粒体功能和线粒体生物发生参数（PGC-1α、NRF2、Tfam）的表达[3]。
在体外，SR 18292（12.5-200μM）处理黑色素瘤A375和WM115贴壁细胞48h，剂量依赖性地降低了细胞的活力、集落形成和迁移，抑制了黑色素瘤细胞球形成能力和ABCG2富集[4]。SR 18292（10、20μM）处理人骨髓源性间充质干细胞（hMSC），显著抑制PGC-1α的蛋白水平并增加GLUT1的蛋白水平，增加了hMSC的葡萄糖摄取率和乳酸生成率[5]。SR 18292（20μM）处理NK细胞48h或10d，可逆转二十二碳六烯酸（DHA）诱导的细胞IFNγ、线粒体质量、膜电位和葡萄糖摄取增加[6]。
在体内，SR 18292（10mg/kg/day）通过腹腔注射治疗镰状细胞病（SCD）小鼠4周，显著减少了小鼠的外周血中不可逆镰状红细胞和网织红细胞数量，改善了红细胞存活率[7]。SR 18292（30μg）通过鞘内注射处理神经性疼痛（PINP）模型大鼠，部分消除了福莫特罗对PINP的镇痛作用[8]。
| Cell experiment [1]: | |
Cell lines | A375 and WM115 adherent cells |
Preparation Method | Cells were treated with SR 18292 (12.5–200μM) for 48 h, cell viability was then evaluated by MTT assay. The medium was then changed with MTT solution (0.5mg/ml) in DMEM or RPMI without phenol red and FBS; cells were incubated at 37°C for 30 min and violet precipitate was dissolved with isopropanol. Absorbance at 550nm was measured through an EnSpire Multimode Plate reader. |
Reaction Conditions | 12.5-200μM; 48h |
Applications | Treatment with SR 18292 reduced the viability of melanoma cells in a dose-dependent manner. |
| Animal experiment [2]: | |
Animal models | Sickle cell disease (SCD) mice |
Preparation Method | SCD mice were randomly divided into the following groups: (1) Control group: treated with an equal amount of saline. (2) SR 18292-treated group: treated with SR 18292 at a dose of 10mg/kg body weight, intraperitoneally injected daily for 4 consecutive weeks. After the 4-week treatment period, the mice were sacrificed, and blood samples, spleen, liver and other organs were collected for analysis to evaluate fetal hemoglobin (HbF) levels, sickle cell ratio and other biomarkers related to SCD. |
Dosage form | 10mg/kg/day; i.p. |
Applications | SR 18292 induces HbF in SCD mice and also reduces organ damage and erythrocyte sickling in mice. |
References: [1] Fontana F, Macchi C, Anselmi M, et al. PGC1-α-driven mitochondrial biogenesis contributes to a cancer stem cell phenotype in melanoma[J]. Biochimica et Biophysica Acta (BBA)-Molecular Basis of Disease, 2024, 1870(1): 166897. [2]Sun Y, Benmhammed H, Al Abdullatif S, et al. PGC-1α agonism induces fetal hemoglobin and exerts antisickling effects in sickle cell disease[J]. Science Advances, 2024, 10(31): eadn8750. | |
| Cas No. | 2095432-55-4 | SDF | |
| 化学名 | 1-[(1,1-dimethylethyl)[(4-methylphenyl)methyl]amino]-3-(1H-indol-4-yloxy)-2-propanol | ||
| Canonical SMILES | CC(C)(C)N(CC(O)COC1=CC=CC2=C1C=CN2)CC3=CC=C(C)C=C3 | ||
| 分子式 | C23H30N2O2 | 分子量 | 366.5 |
| 溶解度 | DMF: 25 mg/ml,DMSO: 25 mg/ml,DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml,Ethanol: 10 mg/ml | 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.7285 mL | 13.6426 mL | 27.2851 mL |
| 5 mM | 0.5457 mL | 2.7285 mL | 5.457 mL |
| 10 mM | 0.2729 mL | 1.3643 mL | 2.7285 mL |
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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 | ||||||||||
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