| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| Other Sizes |
| Targets |
SGK1-IN-3 hydrochloride targets serum and glucocorticoid-regulated kinase 1 (SGK1). SGK1 is a serine/threonine kinase belonging to the AGC kinase family (along with AKT/PKB, PKC, PKA, etc.). SGK1 is activated by various growth factors, hormones, and cellular stresses and plays a role in the regulation of ion channels, cell proliferation, apoptosis, and gene expression. In osteoarthritis, SGK1 is an activator of the beta-catenin pathway and a stimulator of cartilage degradation. Inhibition of SGK1 may protect against cartilage destruction.
|
|---|---|
| ln Vitro |
In vitro, SGK1-IN-3 hydrochloride is a potent inhibitor of SGK1 with an IC50 of <1 microM. The serine/threonine kinase SGK1 is an activator of the beta-catenin pathway and a powerful stimulator of cartilage degradation. The compound is designed to inhibit SGK1 activity, which is upregulated in diseased osteoarthritic cartilage. No specific cellular activity data (e.g., effects on chondrocytes, cartilage matrix degradation, or beta-catenin signaling in cell-based models) are reported in the search results.
|
| ln Vivo |
No specific in vivo activity data for SGK1-IN-3 hydrochloride are reported in the search results. However, as an orally active SGK1 inhibitor, it has potential for evaluation in animal models of osteoarthritis (OA). Standard OA models include surgical destabilization of the medial meniscus (DMM) in mice or rats, or enzymatic induction of OA via intra-articular injection of collagenase. SGK1-IN-3 hydrochloride could be administered orally once daily for 4-8 weeks, and joint tissues would be assessed for cartilage degradation (by histology, OARSI scoring), synovitis, and subchondral bone changes. No specific dosing or efficacy data are provided.
|
| Enzyme Assay |
The binding of SGK1-IN-3 hydrochloride to SGK1 is measured by standard in vitro kinase activity assays using purified recombinant human SGK1 enzyme. The compound is incubated with the kinase, a specific peptide substrate (e.g., derived from GSK-3beta or a synthetic peptide), and ATP (including gamma-32P-ATP for radiometric assays or using non-radioactive ADP-Glo™ assays). After incubation, the amount of phosphorylated peptide is quantified. The IC50 value (reported as <1 microM) is calculated from dose-response curves (0.001-100 microM). Selectivity against related kinases (e.g., AKT1, PKC, PKA, SGK2, SGK3) can be assessed by similar assays. No specific IC50 value is provided beyond <1 microM.
|
| Cell Assay |
No cellular experiments for SGK1-IN-3 hydrochloride are described in the search results. For cellular studies of SGK1 inhibition, human chondrocyte cell lines (e.g., C-28/I2, T/C-28a2, primary human articular chondrocytes) are seeded in 6- or 96-well plates. Cells are treated with SGK1-IN-3 hydrochloride at graded concentrations (0.01-100 microM) for 24-72 hours. Cells are then stimulated with pro-inflammatory cytokines (e.g., IL-1beta (10 ng/mL) or TNF-alpha) to induce catabolic changes. SGK1 activity is assessed by Western blot for phosphorylated SGK1 substrates (e.g., NDRG1 at Thr346). Cartilage degradation markers (e.g., MMP-13, ADAMTS-5, collagen type II, aggrecan) are measured by qPCR or ELISA. beta-catenin signaling is assessed by Western blot for active beta-catenin (non-phosphorylated) or by TOPFlash reporter assay.
|
| Animal Protocol |
No animal experiments for SGK1-IN-3 hydrochloride are described in the search results. For in vivo evaluation of SGK1 inhibition in osteoarthritis, 8-10-week-old male C57BL/6 mice would be used. The destabilization of the medial meniscus (DMM) surgery is performed on the right knee to induce post-traumatic OA, while the left knee is used as a sham control. SGK1-IN-3 hydrochloride would be administered orally by gavage at doses of 10-50 mg/kg once daily for 8-12 weeks. At the study endpoint, knee joints would be harvested, fixed, decalcified, and sectioned for histological analysis. Cartilage degeneration would be assessed using the OARSI scoring system. The expression of SGK1, phosphorylated NDRG1, MMP-13, and aggrecan in articular cartilage would be evaluated by immunohistochemistry.
|
| ADME/Pharmacokinetics |
SGK1-IN-3 hydrochloride (compound 3a) has a molecular formula of C23H21Cl3N₆O3S, with a molecular weight of approximately 583.88 (or similar as reported by suppliers). For storage, the powder should be kept at -20degC sealed, away from moisture and light. For in vitro use, stock solutions in DMSO (10-50 mM) can be stored at -80degC for up to 6 months or at -20degC for 1 month. For in vivo oral administration, it can be formulated in 0.5% methylcellulose/0.1% Tween-80 or 10% DMSO / 40% PEG300 / 5% Tween-80 / 45% saline. Purity is typically ≥98% (HPLC). No detailed PK parameters (oral bioavailability, Cmax, Tmax, half-life) are reported.
|
| Toxicity/Toxicokinetics |
No specific toxicity data for SGK1-IN-3 hydrochloride are reported in the search results. As a research-grade compound, it is not intended for human or veterinary use. Standard laboratory safety precautions for handling chemicals should be followed, including the use of gloves, lab coat, and safety goggles. SGK1 is involved in ion channel regulation and electrolyte balance; systemic inhibition may cause electrolyte disturbances. No LD50 or formal toxicology studies are available.
|
| References | |
| Additional Infomation |
SGK1-IN-3 hydrochloride (compound 3a) is a potent and orally active inhibitor of SGK1. SGK1 (serum and glucocorticoid-regulated kinase 1) is a serine/threonine kinase that is activated by insulin, growth factors, and various hormones. SGK1 plays a key role in regulating ion channels (ENaC, Kv1.3, KCNE1/KCNQ1), cell volume, and gene expression. In osteoarthritis, SGK1 is upregulated and promotes cartilage degradation through activation of the beta-catenin pathway. SGK1 inhibitors have been proposed as potential disease-modifying osteoarthritis drugs (DMOADs). SGK1-IN-3 hydrochloride is for research use only and has not entered clinical trials or received regulatory approval.
|
| Molecular Formula |
C23H21CL3N6O3S
|
|---|---|
| Molecular Weight |
567.88
|
| Appearance |
Solid powder
|
| 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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
|
|---|---|
| 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 | 1.7609 mL | 8.8047 mL | 17.6094 mL | |
| 5 mM | 0.3522 mL | 1.7609 mL | 3.5219 mL | |
| 10 mM | 0.1761 mL | 0.8805 mL | 1.7609 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
