| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg |
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| Targets |
Target: Cathepsin K (CatK), a cysteine protease primarily expressed in osteoclasts. CatK is responsible for the degradation of type I collagen and other bone matrix proteins during bone resorption. By inhibiting CatK, Gü2602 reduces bone resorption activity, making it a potential therapeutic agent for osteoporosis, osteoarthritis, and bone metastasis. Gü2602 binds reversibly to the active site of CatK with a Ki of 0.013 nM for the mature enzyme.
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| ln Vitro |
In vitro, Gü2602 is a potent, reversible cathepsin K (CatK) inhibitor with a Ki of 0.013 nM for mature CatK (mCatK). It suppresses the autocatalytic activation of the cathepsin K zymogen, preventing the conversion of procathepsin K to its active form. Detailed IC50 values for inhibition of collagen degradation in osteoclast cultures have not been publicly disclosed. No significant cytotoxicity is reported at effective concentrations.
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| ln Vivo |
No in vivo efficacy data have been published specifically for Gü2602 in animal models. Based on its potent inhibition of CatK, the compound is expected to suppress bone resorption in animal models of osteoporosis (ovariectomized rats), reduce bone loss in models of periodontitis, and inhibit osteolytic bone metastasis in cancer models. In vivo PK and efficacy studies are likely ongoing.
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| Enzyme Assay |
For cell-free CatK enzyme activity assays: recombinant human mature CatK (mCatK, 50-100 ng) is incubated with varying concentrations of Gü2602 (0-10 nM) and a fluorogenic peptide substrate (e.g., Z-Leu-Arg-AMC or Z-Phe-Arg-AMC) in assay buffer (100 mM MES pH 5.5, 2 mM DTT, 2 mM EDTA) at 37degC for 30-60 min. Fluorescence is measured at excitation 380 nm, emission 460 nm. The Ki (0.013 nM) is calculated from dose-response curves using Morrison equation for tight-binding inhibitors.
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| Cell Assay |
For cell-based assays: primary mouse or human osteoclasts differentiated from bone marrow macrophages (BMMs) or RAW264.7 cells using RANKL and M-CSF are seeded in 96-well plates. Cells are treated with Gü2602 (0.001-10 nM, 2-7 days). CatK activity is measured using a fluorogenic substrate in cell lysates. Bone resorption is assessed by culturing osteoclasts on dentine slices or calcium phosphate-coated plates and measuring resorption pit area by microscopy or colorimetric assay for released calcium. Cell viability is measured by MTT or CellTiter-Glo.
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| Animal Protocol |
For in vivo animal studies: potential protocol involves ovariectomized (OVX) rats or mice as a model of postmenopausal osteoporosis. After ovariectomy, animals are allowed to lose bone for 4-8 weeks, then treated with Gü2602 orally (1-10 mg/kg) daily for 6-12 weeks. Bone mineral density (BMD) is measured by DEXA or micro-CT. Bone resorption markers (e.g., CTX-1, NTX-1) in serum or urine are measured by ELISA. Femurs and tibiae are harvested for micro-CT analysis (trabecular bone volume, thickness, and separation) and histomorphometry (TRAP staining for osteoclasts).
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| ADME/Pharmacokinetics |
PK properties of Gü2602: For a small molecule CatK inhibitor (MW 318.37, LogP 2.5, solubility in DMSO 66.67 mg/mL), predicted PK in rodents after oral administration: moderate bioavailability (30-50%), Tmax 1-2 h, plasma half-life 4-8 h. Volume of distribution is moderate (2-4 L/kg). Metabolism is primarily via CYP450 enzymes. The compound can be formulated in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% saline for oral or IP administration.
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| Toxicity/Toxicokinetics |
No toxicity data have been reported for Gü2602. CatK inhibitors are generally well-tolerated in animal studies. Off-target effects may include potential skin lesions and arterial calcification observed with some CatK inhibitors, but these are not reported for Gü2602. The compound is for research use only and not for human consumption.
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| References | |
| Additional Infomation |
Gü2602 is a research compound not yet approved for clinical use. It is a valuable tool for studying CatK function in bone resorption and other CatK-mediated processes. It has potential applications in osteoporosis research, bone metastasis, osteoarthritis, and periodontitis. The compound is structurally distinct from other CatK inhibitors such as odanacatib. It may also be used as a reference standard in CatK inhibitor screening.
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| Molecular Formula |
C16H22N4O3
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|---|---|
| Molecular Weight |
318.370883464813
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| Exact Mass |
318.169
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| CAS # |
1627094-88-5
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| PubChem CID |
118716318
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| Appearance |
Off-white to light yellow solid powder
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| LogP |
2.5
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
23
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| Complexity |
458
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N(C(OC(C)(C)C)=O)N(C#N)CC(N(C)CC1=CC=CC=C1)=O
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| InChi Key |
LHJKRUYOLRIDGD-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C16H22N4O3/c1-16(2,3)23-15(22)18-20(12-17)11-14(21)19(4)10-13-8-6-5-7-9-13/h5-9H,10-11H2,1-4H3,(H,18,22)
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| Chemical Name |
tert-butyl N-[[2-[benzyl(methyl)amino]-2-oxoethyl]-cyanoamino]carbamate
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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 (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)
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| Solubility (In Vitro) |
DMSO : ~66.67 mg/mL (~209.41 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (7.85 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. Solubility in Formulation 2: ≥ 2.5 mg/mL (7.85 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 of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.1410 mL | 15.7050 mL | 31.4100 mL | |
| 5 mM | 0.6282 mL | 3.1410 mL | 6.2820 mL | |
| 10 mM | 0.3141 mL | 1.5705 mL | 3.1410 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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