SR 18292 |
| Catalog No.GC18269 |
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.
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| Chemical Name | 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 | ||
| Formula | C23H30N2O2 | M.Wt | 366.5 |
| Solubility | DMF: 25 mg/ml,DMSO: 25 mg/ml,DMSO:PBS (pH 7.2) (1:2): 0.33 mg/ml,Ethanol: 10 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
|
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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Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
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Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 23 reference(s) in Google Scholar.)
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