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Purity: ≥98%
GSK2795039 is a novel and potent small molecule NADPH oxidase 2 inhibitor with a mean pIC50 of 6 in different cell-free assays.
| Targets |
- NADPH Oxidase 2 (NOX2)：GSK2795039 is a selective small molecule inhibitor of NOX2, with an IC₅₀ of 0.537 μM in cell-free assays for NOX2-mediated reactive oxygen species (ROS) production and an IC₅₀ of 0.251 μM for NADPH consumption. It shows >1,000-fold selectivity over other NOX isoforms (NOX1, NOX3, NOX4, NOX5) and enzymes like xanthine oxidase and PKCβ. [1]
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| ln Vitro |
- NOX2 inhibition and ROS suppression：In cell-free systems, GSK2795039 (0.1–10 μM) dose-dependently inhibits NOX2-mediated superoxide generation (measured by cytochrome c reduction) and NADPH oxidation. In activated microglia treated with iron (Fe²⁺), GSK2795039 (1–10 μM) reduces ROS production by 60–80%, as detected by DCFH-DA fluorescence. [1][2]
- Cell signaling modulation：In LPS-stimulated U937 monocytes, GSK2795039 (5 μM) downregulates NOX2 subunit (p47phox) phosphorylation and decreases phosphorylation of MAPKs (ERK1/2, p38) by 40–50%, as measured by Western blot. [1] Reduces the presence of caspase-3-positive PC12 cells and the combined effect of FeSO4 and LPS on enhanced levels of apoptosis when GSK2795039 (25 μM; 24 hours) is administered [2]. |
| ln Vivo |
- Reduction of oxidative stress in cerebral hemorrhage：In a mouse model of intracerebral hemorrhage, GSK2795039 (100 mg/kg, i.p., daily for 7 days) reduces brain malondialdehyde (MDA) levels by 45% (a marker of lipid peroxidation) and decreases TUNEL-positive apoptotic cells by 50% compared to vehicle controls. Neurological function, assessed by the Garcia score, improves by 30%. [1]
- Cardioprotection in doxorubicin-induced toxicity：In rats with doxorubicin-induced cardiomyopathy, co-administration of GSK2795039 (50 mg/kg, oral, daily) preserves left ventricular ejection fraction (LVEF) by 25% and reduces myocardial fibrosis by 40% (Masson’s trichrome staining) compared to doxorubicin alone. [1] GSK2795039 (ip; 100 mg/kg; one hour ago) lowers serum amylase levels brought on by systemic cerulein injection and decreases activity in a mouse model of acute pancreatitis [1]. |
| Enzyme Assay |
- NOX2 activity assay：
1. Recombinant NOX2 enzyme (isolated from human neutrophils) is incubated with NADPH (100 μM) and GSK2795039 (0.01–10 μM) in phosphate buffer.
2. Superoxide production is measured via cytochrome c reduction (550 nm absorbance) or lucigenin chemiluminescence.
3. IC₅₀ values are calculated based on dose-response curves. [1]
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| Cell Assay |
Apoptosis analysis[2]
Cell Types: PC12 Cell Tested Concentrations: 25 μM Incubation Duration: 24 hrs (hours) Experimental Results: diminished apoptosis in PC12 cells. - ROS detection in microglia： 1. BV-2 microglia are pretreated with GSK2795039 (0.1–10 μM) for 1 hour, then stimulated with Fe²⁺ (50 μM) for 30 minutes. 2. Intracellular ROS is measured by flow cytometry using DCFH-DA (10 μM) staining. 3. Inhibition of ROS is quantified as the percentage reduction compared to Fe²⁺-treated controls. [2] - NOX2 subunit expression： 1. LPS-activated THP-1 macrophages are treated with GSK2795039 (5 μM) for 24 hours. 2. Western blot analysis detects reduced expression of NOX2 subunits (p22phox, gp91phox) and phosphorylated p47phox. [1] |
| Animal Protocol |
Animal/Disease Models: C57BL6 mice [1]
Doses: 100 mg/kg Route of Administration: intraperitoneal (ip) injection; 100 mg/kg; 1 hour before Experimental Results: Causes a 50% reduction in serum amylase activity levels. - Cerebral hemorrhage model： 1. Mice undergo collagenase-induced intracerebral hemorrhage. 2. GSK2795039 (100 mg/kg) is administered intraperitoneally daily for 7 days. 3. Neurological deficits are assessed using the Garcia score, and brain tissue is analyzed for malondialdehyde (MDA) levels and TUNEL-positive cells. [1] - Doxorubicin-induced cardiomyopathy model： 1. Rats receive doxorubicin (2 mg/kg, i.p.) weekly for 4 weeks. 2. GSK2795039 (50 mg/kg, oral) is co-administered daily. 3. Cardiac function is evaluated by echocardiography, and myocardial fibrosis is assessed by Masson’s trichrome staining. [1] |
| ADME/Pharmacokinetics |
- Oral bioavailability：In rats, GSK2795039 (50 mg/kg, oral) achieves Cmax of 1.8 μg/mL at 1.5 hours, with oral bioavailability of ~35%. [1]
- Tissue distribution：In mice, the compound accumulates in the brain (brain/plasma ratio = 2.5:1) and heart (heart/plasma ratio = 3:1) after intravenous administration. [1] - Metabolism：Primarily metabolized by hepatic CYP3A4, with <10% excreted unchanged in urine. [1] |
| References |
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| Additional Infomation |
- Mechanism of action：GSK2795039 binds to the p47phox subunit of NOX2, preventing its translocation to the cell membrane and inhibiting NADPH-dependent superoxide production. [1]
- Therapeutic potential：Investigated for neurodegenerative diseases (e.g., Parkinson’s disease), cardiovascular disorders (e.g., atherosclerosis), and inflammatory conditions (e.g., rheumatoid arthritis). [1][2] |
| Molecular Formula |
C23H26N6O2S
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|---|---|
| Molecular Weight |
450.5565
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| Exact Mass |
450.183
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| Elemental Analysis |
C, 61.31; H, 5.82; N, 18.65; O, 7.10; S, 7.12
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| CAS # |
1415925-18-6
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| PubChem CID |
71090129
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| Appearance |
White to yellow solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
691.5±65.0 °C at 760 mmHg
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| Flash Point |
372.0±34.3 °C
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| Vapour Pressure |
0.0±2.2 mmHg at 25°C
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| Index of Refraction |
1.707
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| LogP |
3.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
32
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| Complexity |
773
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| Defined Atom Stereocenter Count |
0
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| SMILES |
S(C1C([H])=C([H])N(C([H])([H])[H])N=1)(N([H])C1C([H])=C([H])N=C2C=1C(=C([H])N2C([H])(C([H])([H])[H])C([H])([H])[H])C1C([H])=C([H])C2C([H])([H])C([H])([H])N(C([H])([H])[H])C=2C=1[H])(=O)=O
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| InChi Key |
FMWVTCZKCXPKFW-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C23H26N6O2S/c1-15(2)29-14-18(17-6-5-16-8-11-27(3)20(16)13-17)22-19(7-10-24-23(22)29)26-32(30,31)21-9-12-28(4)25-21/h5-7,9-10,12-15H,8,11H2,1-4H3,(H,24,26)
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| Chemical Name |
N-(1-Isopropyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1-methyl-1H-pyrazole-3-sulfonamide
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| Synonyms |
GSK-2795039; GSK 2795039; GSK2795,039; 1415925-18-6; GSK-2795,039; N-(1-Isopropyl-3-(1-methylindolin-6-yl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1-methyl-1H-pyrazole-3-sulfonamide; 1-methyl-N-[3-(1-methyl-2,3-dihydroindol-6-yl)-1-propan-2-ylpyrrolo[2,3-b]pyridin-4-yl]pyrazole-3-sulfonamide; CHEMBL5424942; orb1308249; SCHEMBL14158596; GSK2795039
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO : ~100 mg/mL (~221.95 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 10 mg/mL (22.19 mM) in 20% DMSO, 20% Tween 80, 60% polyethylene glycol 200 (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
Solubility in Formulation 2: 6.67 mg/mL (14.80 mM) in 15% Cremophor EL + 85% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.5 mg/mL (5.55 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. Solubility in Formulation 4: ≥ 2.5 mg/mL (5.55 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 corn oil and mix evenly. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.2195 mL | 11.0973 mL | 22.1946 mL | |
| 5 mM | 0.4439 mL | 2.2195 mL | 4.4389 mL | |
| 10 mM | 0.2219 mL | 1.1097 mL | 2.2195 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.
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