| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 25mg |
|
||
| 50mg |
|
||
| Other Sizes |
Purity: ≥98%
| Targets |
Reactive Oxygen Species; ERRγ (IC50 = 79 nM)
Estrogen-related receptor γ (ERRγ); does not interact with other nuclear receptors including ERRα or ERα. |
|---|---|
| ln Vitro |
GSK5182 (0-20 μM; 0-hours; PLC/PRF/5 cells) treatment reduces the number of proliferating PLC/PRF/5 cells significantly and dose-dependently[1].
GSK5182 (0-20 μM; 24 hours; PLC/PRF/5 cells) treatment also results in a decrease in the amount of phosphorylated retinoblastoma protein (p-pRb) and a dose-dependent increase in the expression of p21 and p27[1]. GSK5182 (10-20 μM; PLC/PRF/5 cells) treatment causes a dose-dependent decrease in the proportion of cells in the S phase by causing cell cycle arrest at the G1 phase[1]. GSK5182 inhibits ERRγ with an IC50 of 79 nM in biochemical assays. It shows 68% inhibition at 1 μM in reporter assays and effectively inhibits ERRγ-dependent gene expression in cultures at 1-10 μM. It does not inhibit 100 nM estradiol-induced reporter activity up to 1 μM for ERRα, demonstrating high selectivity. GSK5182 also induces reactive oxygen species generation in hepatocellular carcinoma cells. |
| ln Vivo |
GSK5182 (40 mg/kg; intraperitoneal injection; every day; 25 or 30 days; db/db mice, diet-induced obesity mice) specifically inhibits ERRγ's transcriptional activity and reduces the amount of glucose produced in the liver by blocking hepatic gluconeogenesis. GSK5182 inhibits the hepatic gluconeogenesis program in mouse models to produce anti-diabetic effects. GSK5182 primarily normalizes hyperglycemia by preventing the liver from producing glucose[3].
In vivo, GSK5182 (40 mg/kg, i.p., daily for 25-30 days) normalizes hyperglycemia in db/db and diet-induced obesity mice primarily through inhibition of hepatic glucose production via suppression of gluconeogenesis. It also significantly reduces cartilage degeneration in ERRγ-overexpressing mice administered intra-articular Ad-Esrrg. Doses range from 10-80 mg/kg i.p. or p.o. in rodents. |
| Enzyme Assay |
ERRγ inverse agonist activity is assessed using a reporter assay in HEK293 cells transfected with ERRγ and a luciferase reporter; compounds are incubated for 24 h and luciferase activity measured. Binding affinity is evaluated by surface plasmon resonance or competitive binding assays using recombinant ERRγ ligand-binding domain. IC50 values are calculated from dose-response curves.
|
| Cell Assay |
The experiment involved culturing mouse articular chondrocytes (3×105) for two days, followed by an infection with different Ad-Esrrg adenovirus concentrations [200 800 MOI (multiplicity of infection)] for two hours, and an additional twenty-four hours of culture in the presence or absence of GSK5182 (2.5-10 μM). Several inflammatory cytokines, including TNF-α (10-50 ng/mL), IL-6 (10-50 ng/mL), and IL-1β (0.1-1 ng/mL), were applied to the cells for a full day.
Cellular activity is evaluated in mouse articular chondrocytes or hepatocellular carcinoma cell lines. Cells are treated with GSK5182 (1-10 μM) for 24-48 h, then analyzed for ERRγ-dependent gene expression by qRT-PCR, reactive oxygen species production using fluorescent probes, or cell proliferation assays. Inhibition of pro-inflammatory cytokine-induced catabolic factors is also measured. |
| Animal Protocol |
db/db mice (male, 7-12-week-old), diet-induced obesity (DIO) mice[3]
40 mg/kg Intraperitoneal injection; every day; 30 days for db/db mice, 25 days for DIO mice In vivo efficacy is studied in male db/db mice (7-12 weeks old) and diet-induced obesity mice. GSK5182 is administered at 40 mg/kg via intraperitoneal injection daily for 25-30 days. Blood glucose levels, hepatic glucose production, and gluconeogenic gene expression are measured. In cartilage studies, mice receive intra-articular Ad-Esrrg followed by GSK5182 treatment and cartilage degeneration is assessed histologically. |
| ADME/Pharmacokinetics |
GSK5182 is orally bioavailable and shows good plasma exposure in mice. It is metabolized by human liver microsomes and recombinant cytochrome P450 enzymes, with N-oxidation being a major metabolic pathway. Pharmacokinetic studies in mice show dose-dependent plasma concentrations. The compound has a predicted logP of 5.3 and is soluble in DMSO and ethanol.
|
| Toxicity/Toxicokinetics |
Toxicological data indicate GSK5182 is a hazardous substance containing a pharmaceutically active ingredient. It poses risks of serious eye damage (R41) and toxicity with danger of serious health damage upon prolonged exposure (R48). Under fire conditions, it may decompose and emit toxic fumes. Avoid release into the environment.
|
| References |
|
| Additional Infomation |
estrogen-associated receptor gamma inverse agonists
GSK5182 is a research tool compound not approved for clinical use. It is a tamoxifen analog developed as a chemical probe for studying ERRγ biology. The compound has been investigated in preclinical models of type 2 diabetes, liver cancer, and osteoarthritis. Its mechanism involves inverse agonism of ERRγ, leading to suppression of gluconeogenic gene expression and inhibition of cancer cell proliferation. |
| Molecular Formula |
C27H31NO3
|
|---|---|
| Molecular Weight |
417.55
|
| Exact Mass |
417.23
|
| Elemental Analysis |
C, 77.67; H, 7.48; N, 3.35; O, 11.49
|
| CAS # |
877387-37-6
|
| Related CAS # |
(E/Z)-GSK5182;2699724-40-6
|
| PubChem CID |
6852176
|
| Appearance |
White to off-white solid powder
|
| Density |
1.132±0.06 g/cm3(Predicted)
|
| Boiling Point |
567.6±50.0 °C(Predicted)
|
| LogP |
5.9
|
| Hydrogen Bond Donor Count |
2
|
| Hydrogen Bond Acceptor Count |
4
|
| Rotatable Bond Count |
10
|
| Heavy Atom Count |
31
|
| Complexity |
525
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
C(/C1C=CC(O)=CC=1)(\C1C=CC(OCCN(C)C)=CC=1)=C(\C1C=CC=CC=1)/CCCO
|
| InChi Key |
ZVSFNBNLNLXEFQ-RQZHXJHFSA-N
|
| InChi Code |
InChI=1S/C27H31NO3/c1-28(2)18-20-31-25-16-12-23(13-17-25)27(22-10-14-24(30)15-11-22)26(9-6-19-29)21-7-4-3-5-8-21/h3-5,7-8,10-17,29-30H,6,9,18-20H2,1-2H3/b27-26-
|
| Chemical Name |
4-[(Z)-1-[4-[2-(dimethylamino)ethoxy]phenyl]-5-hydroxy-2-phenylpent-1-enyl]phenol
|
| Synonyms |
GSK5182; GSK-5182; GSK 5182
|
| 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: 25~84 mg/mL (59.9~201.2 mM)
Ethanol: ~84 mg/mL (~201.2 mM) |
|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3949 mL | 11.9746 mL | 23.9492 mL | |
| 5 mM | 0.4790 mL | 2.3949 mL | 4.7898 mL | |
| 10 mM | 0.2395 mL | 1.1975 mL | 2.3949 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.
|
|
|
|
|
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
COA
