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| Targets |
NOD2
Nucleotide-binding oligomerization domain 2 (NOD2), an intracellular pattern recognition receptor that recognizes muramyl dipeptide (MDP) from bacterial peptidoglycan. GSK717 is a potent and selective NOD2 inhibitor. It inhibits MDP-induced NOD2-mediated signaling and IL-8 secretion with an IC50 of 400 nM. GSK717 blocks the synergy between NOD2 and TLR2 but does not affect NOD1, TNFR1, or TLR2-mediated responses, demonstrating its selectivity for NOD2. |
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| ln Vitro |
GSK717 prevents NOD2 and TLR2 from working together. NOD1, TNFR1, and TLR2-mediated responses are unaffected by GSK717. Primary human monocytes activated with MDP produce less IL-8, IL-6, TNFα, and IL-1β when GSK717 (5 μM) is present [1].
GSK717 inhibits MDP-induced NOD2-mediated signaling in vitro. In HEK293/hNOD2 cells stimulated with MDP, GSK717 inhibits IL-8 secretion with an IC50 of 400 nM. The compound does not affect NOD1, TNFR1, or TLR2-mediated responses, confirming its selectivity for NOD2. GSK717 also blocks the synergy between NOD2 and TLR2, suggesting that it can modulate the crosstalk between these two innate immune pathways. |
| ln Vivo |
In vivo, GSK717 is expected to modulate NOD2-mediated inflammatory responses based on its in vitro activity. By inhibiting NOD2 signaling, the compound may reduce the production of pro-inflammatory cytokines and chemokines in response to bacterial products. However, detailed in vivo efficacy data in animal models of NOD2-associated diseases are limited in the available literature.
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| Enzyme Assay |
The in vitro enzyme/receptor binding (cell-free) assay for GSK717 is not a typical enzyme inhibition assay, as NOD2 is not an enzyme but a pattern recognition receptor. Instead, the compound's activity is assessed in cell-based assays measuring NOD2-mediated signaling. The binding of GSK717 to NOD2 could potentially be assessed using surface plasmon resonance or other biophysical techniques, but such assays are not described in the available literature.
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| Cell Assay |
In vitro cellular assays for GSK717 are performed using HEK293 cells engineered to express human NOD2 (HEK293/hNOD2 cells). Cells are stimulated with muramyl dipeptide (MDP) in the presence of varying concentrations of GSK717. NOD2-mediated signaling is assessed by measuring IL-8 secretion using ELISA. The IC50 for inhibition of IL-8 secretion is determined from dose-response curves. Selectivity is confirmed by testing the compound against NOD1, TNFR1, and TLR2-mediated responses.
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| Animal Protocol |
In vivo animal experiments for GSK717 would typically be conducted in rodent models of NOD2-associated diseases, such as inflammatory bowel disease or Blau syndrome. The compound would be administered via oral gavage or intraperitoneal injection. Pharmacodynamic endpoints would include the measurement of inflammatory cytokine levels (IL-8, TNF-α) in serum or tissues, assessment of NOD2 signaling pathway activation, and histopathological evaluation of tissue inflammation.
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| ADME/Pharmacokinetics |
Pharmacokinetic data for GSK717 are limited. As a small molecule with a molecular weight of 452.55 g/mol and a molecular formula of C28H28N4O2, the compound is expected to have moderate oral bioavailability and tissue distribution. However, detailed pharmacokinetic parameters such as half-life, Cmax, AUC, and clearance have not been extensively reported. Further studies would be required to fully characterize its ADME properties.
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| Toxicity/Toxicokinetics |
Toxicology data for GSK717 are limited. The compound is used for research purposes only and is not approved for human use. No significant toxicities have been reported in the available literature. As a NOD2 inhibitor, the compound may have immunomodulatory effects that could impact host defense against bacterial infections. Careful evaluation of safety and potential off-target effects would be required for therapeutic development.
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| References | |
| Additional Infomation |
GSK717 (CAS: 1595278-21-9) has a molecular formula of C28H28N4O2 and a molecular weight of 452.55. It is a potent and selective NOD2 inhibitor that inhibits MDP-induced NOD2-mediated signaling and IL-8 secretion with an IC50 of 400 nM. GSK717 blocks NOD2-TLR2 synergy but does not affect NOD1, TNFR1, or TLR2-mediated responses. The compound is not approved for human use and is intended for research purposes only.
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| Molecular Formula |
C28H28N4O2
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|---|---|
| Molecular Weight |
452.547526359558
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| Exact Mass |
452.221
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| CAS # |
1595278-21-9
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| PubChem CID |
102369397
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| Appearance |
White to off-white solid powder
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| LogP |
4.7
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
34
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| Complexity |
709
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| Defined Atom Stereocenter Count |
0
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| SMILES |
O=C(CN1C2C=CC=CC=2N=C1CCN(C(C1C=CC=CC=1)=O)C)NC1C=CC2=C(C=1)CCC2
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| InChi Key |
YDOATJUIIFWTKQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C28H28N4O2/c1-31(28(34)21-8-3-2-4-9-21)17-16-26-30-24-12-5-6-13-25(24)32(26)19-27(33)29-23-15-14-20-10-7-11-22(20)18-23/h2-6,8-9,12-15,18H,7,10-11,16-17,19H2,1H3,(H,29,33)
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| Chemical Name |
N-[2-[1-[2-(2,3-dihydro-1H-inden-5-ylamino)-2-oxoethyl]benzimidazol-2-yl]ethyl]-N-methylbenzamide
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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: 250 mg/mL (552.43 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.60 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 20.8 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: ≥ 2.08 mg/mL (4.60 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 20.8 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: ≥ 2.08 mg/mL (4.60 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 | 2.2097 mL | 11.0485 mL | 22.0970 mL | |
| 5 mM | 0.4419 mL | 2.2097 mL | 4.4194 mL | |
| 10 mM | 0.2210 mL | 1.1049 mL | 2.2097 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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