| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Cathepsin C
Cathepsin C (CTSC / DPP-1) |
|---|---|
| ln Vitro |
GSK-2793660 inhibits Cathepsin C with high potency (IC50 of 0.43-1 nM). It is an irreversible inhibitor. By blocking Cathepsin C, it prevents the activation of downstream neutrophil serine proteases, including neutrophil elastase, cathepsin G, and proteinase-3.
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| ln Vivo |
The dipeptidyl peptidase I enzyme, or cathepsin C, is inhibited by GSK-2793660. It is used in the treatment of bronchiectasis, anti-neutrophil cytoplasmic autoantibody (ANCA)-associated vasculitis, and cystic fibrosis[1].
GSK-2793660 is an orally active compound. It has been used in research for the potential treatment of cystic fibrosis, non-cystic fibrosis bronchiectasis, and ANCA-associated vasculitis. In vivo studies have shown target engagement and reduction of active NSPs. |
| Enzyme Assay |
Cathepsin C activity is measured using a fluorogenic substrate such as Gly-Phe-AMC. The compound is pre-incubated with the enzyme in a buffer (e.g., 50 mM MES, pH 6.5, 50 mM NaCl, 5 mM DTT) at room temperature for 10 minutes. The reaction is initiated by adding the substrate, and fluorescence (Ex/Em=380/460 nm) is monitored.
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| Cell Assay |
General cellular protocols use THP-1 or U937 cells, which express cathepsin C. Cells are treated with the compound for various times, then lysed. Cathepsin C activity in the lysates is measured using a fluorogenic substrate. The effect on downstream NSP activity can be measured using selective substrates (e.g., MeOSuc-AAPV-AMC for neutrophil elastase).
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| Animal Protocol |
A typical in vivo protocol uses a mouse model of LPS-induced lung inflammation. GSK-2793660 is administered orally at various doses before LPS challenge. Bronchoalveolar lavage fluid is collected to measure NSP activity and inflammatory markers. Neutrophil counts and cytokine levels are assessed to determine efficacy.
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| ADME/Pharmacokinetics |
GSK-2793660 is orally bioavailable with moderate half-life. It is an irreversible inhibitor, leading to prolonged pharmacodynamic effects even after the compound is cleared. In a Phase 1 clinical study, skin desquamation (peeling) was noted as an adverse effect, which ultimately led to the termination of its clinical development.
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| Toxicity/Toxicokinetics |
In a Phase 1 clinical study (NCT02058407), drug-related adverse effects included epidermal desquamation on palmar and plantar surfaces, which led to the termination of GSK-2793660 development. No other severe toxicities were reported. Specific preclinical toxicology data is not publicly available.
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| References | |
| Additional Infomation |
GSK-2793660 was a clinical-stage drug candidate that reached Phase 1 trials for bronchiectasis. Its development was terminated due to adverse effects of skin desquamation. It serves as a research tool for studying the role of cathepsin C and neutrophil serine proteases in inflammatory diseases.
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| Molecular Formula |
C20H28CLN3O3
|
|---|---|
| Molecular Weight |
393.90762424469
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| Exact Mass |
393.181
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| CAS # |
1613458-78-8
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| Related CAS # |
GSK-2793660 free base;1613458-70-0
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| PubChem CID |
74766536
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
5
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| Heavy Atom Count |
27
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| Complexity |
542
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| Defined Atom Stereocenter Count |
1
|
| SMILES |
CC[C@@H](/C=C/C(=O)N1CCC2=CC=CC=C21)NC(=O)C3(CCOCC3)N.Cl
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| InChi Key |
WZTHSMHCYITKEX-YNOPKORFSA-N
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| InChi Code |
InChI=1S/C20H27N3O3.ClH/c1-2-16(22-19(25)20(21)10-13-26-14-11-20)7-8-18(24)23-12-9-15-5-3-4-6-17(15)23;/h3-8,16H,2,9-14,21H2,1H3,(H,22,25);1H/b8-7+;/t16-;/m0./s1
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| Chemical Name |
4-amino-N-[(E,3S)-6-(2,3-dihydroindol-1-yl)-6-oxohex-4-en-3-yl]oxane-4-carboxamide;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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 (253.87 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.35 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 (6.35 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 (6.35 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 | 2.5387 mL | 12.6933 mL | 25.3865 mL | |
| 5 mM | 0.5077 mL | 2.5387 mL | 5.0773 mL | |
| 10 mM | 0.2539 mL | 1.2693 mL | 2.5387 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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