| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| 250mg |
|
||
| 500mg |
|
||
| Other Sizes |
|
Purity: ≥98%
GSK4716 is a novel, potent and selective agonist for the beta and gamma estrogen-related receptors (ERRβ and ERRγ). GSK4716, an ERRbeta/gamma agonist, significantly increased the expression of GRalpha (isoform D) protein in differentiated skeletal muscle cells. Following GSK4716 treatment, quantitative RT-PCR (Q-RT-PCR) analysis demonstrated induction of the mRNAs encoding the glucocorticoid receptor (GR), 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1), the enzyme that changes dormant cortisone into cortisol, and hexose-6-phosphate dehydrogenase expression (H6PDH), which promotes oxoreduction by 11beta-HSD1. Additionally, candidate-based expression profiling showed that GSK4716-treated cells induce the mRNAs encoding GR target genes that have been characterized, such as C/EBP, ApoD, and monoamine oxidase-A (MAO-A). These observations are supported by the fact that mRNAs encoding GR, 11betaHSD1, and GR target gene(s) were less expressed when the mRNA encoding ERRgamma (but not ERRalpha and beta) was suppressed via siRNA. Similar to this, skeletal muscle cells treated with diethylstilbestrol (DES), an antagonist of both ERgamma and ERalpha, showed reduced expression of the gene responsible for glucocorticoid responses. That's right, we saw that GSK4716 required GR in order to trans-activate GRE-TK-LUC. The regulatory overlap between ERRgamma and GR signaling in skeletal muscle cells is highlighted by this study, which also implies that the ERRgamma agonist affects the expression of important genes that regulate GR signaling and the expression of glucocorticoid-sensitive genes.
| Targets |
ERRβ/γ
|
|---|---|
| ln Vitro |
Immunoreactivity of the GRα-D isoform is robustly and reproducibly increased when differentiated C2C12 cells are treated with the ERRβ/γ agonist for two to four hours (compared to vehicle). Research shows that treatment with GSK4716, an ERRβ/γ agonist, significantly increases the expression of MAO-A mRNA. Additionally, GSK4716 is observed to induce the expression of mRNAs encoding PGC-1β, a key regulator of many metabolic genes, and Peroxisome Proliferator-Activated Receptor-γcoactivator 1α (PGC-1α), which have been identified as direct coactivators for the ERR family. In line with the documented function of ERRγ in cardiac metabolism, GSK4716 promotes the expression of PGC-1 and fatty acid oxidation-related genes[1]. GSK4716, an ERRβ/γ agonist, causes a coordinated upregulation of Ppargc1a, Ppargc1b, and the Esrr genes in primary mouse myotubes. Moreover, GSK4716 also induces the genes Cpt1b, Atp5b, and Idh3, which are involved in important mitochondrial pathways. GSK4716 also raises the levels of cytochrome c protein and citrate synthase activity[2].
|
| Cell Assay |
Mouse C2C12 myoblasts that are actively growing are cultivated and kept in DMEM that has been enhanced with 10% heat-inactivated serum supreme. Myoblasts are differentiated into post-mitotic, multi-nucleated myotubes by withholding mitogens (DMEM enriched with 2% horse serum) for a duration of four days. After one day of treatment with either vehicle (DMSO) or the ERRβ/γ agonist GSK4716, RNA is extracted and processed from C2C12 myotubes[1].
|
| References |
|
| Molecular Formula |
C17H18N2O2
|
|---|---|
| Molecular Weight |
282.3370
|
| Exact Mass |
282.14
|
| Elemental Analysis |
C, 72.32; H, 6.43; N, 9.92; O, 11.33
|
| CAS # |
101574-65-6
|
| Related CAS # |
101574-65-6
|
| Appearance |
Solid powder
|
| SMILES |
CC(C)C1=CC=C(C=C1)/C=N/NC(=O)C2=CC=C(C=C2)O
|
| InChi Key |
IKPPIUNQWSRCOZ-WOJGMQOQSA-N
|
| InChi Code |
InChI=1S/C17H18N2O2/c1-12(2)14-5-3-13(4-6-14)11-18-19-17(21)15-7-9-16(20)10-8-15/h3-12,20H,1-2H3,(H,19,21)/b18-11+
|
| Chemical Name |
4-hydroxy-N-[(E)-(4-propan-2-ylphenyl)methylideneamino]benzamide
|
| Synonyms |
GSK 4716; GSK-4716; GSK4716
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: ~56 mg/mL (~198.3 mM)
Ethanol: ~56 mg/mL (~198.3 mM) |
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.85 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.5 mg/mL (8.85 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (8.85 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.5418 mL | 17.7091 mL | 35.4183 mL | |
| 5 mM | 0.7084 mL | 3.5418 mL | 7.0837 mL | |
| 10 mM | 0.3542 mL | 1.7709 mL | 3.5418 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
 Primary mouse myotubes were treated with ERRβ/γ agonist, GSK4716 (10 μm), for 48 h.J Biol Chem.2010 Jul 16;285(29):22619-29. |
|---|
 ERRγ heterozygous mice have lower exercise capacity and impaired mitochondrial oxidative metabolism.J Biol Chem.2010 Jul 16;285(29):22619-29. |
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA