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| Targets |
CL82198 targets MMP-13, a member of the matrix metalloproteinase family that plays a key role in the degradation of extracellular matrix components, particularly collagen type II. MMP-13 is an important target in osteoarthritis, as its activity contributes to the breakdown of cartilage. CL82198 acts as a selective inhibitor, binding to the S1' pocket of MMP-13 without metal chelation. This unique binding mode is responsible for its selectivity for MMP-13 over other MMPs. By inhibiting MMP-13, the compound prevents the degradation of cartilage and may slow the progression of osteoarthritis.
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| ln Vitro |
Significantly less LS174 cell migration occurs when CL-82198 (10 μM) is applied for 24 hours [1]. In hepatic stellate cells, CL-82198 lowers the amounts of TGF-β1 and CTGF [3].
In vitro, CL82198 has been shown to be a potent and selective inhibitor of MMP-13. It inhibits 89% of MMP-13 activity at 10 ug/mL. The compound shows no activity against MMP-1, MMP-9, or TACE, confirming its selectivity. CL82198 significantly reduces the migration of LS174 cells by 55% at 10 uM. These in vitro activities have been demonstrated using purified enzymes and fluorogenic substrates. The compound's selectivity for MMP-13 is attributed to its binding to the entire S1' pocket of the enzyme. |
| ln Vivo |
MLI-induced osteoarthritis is prevented and its progression is impeded by CL82198 (1–10 mg/kg; intraperitoneal injection; every other day for 12 weeks) [4].
In vivo, CL82198 has been shown to prevent and decelerate the progression of osteoarthritis in animal models. In a mouse model of osteoarthritis induced by medial meniscal ligament injury (MLI), administration of CL82198 prevented and decelerated osteoarthritis progression. These results demonstrate the potential of MMP-13 inhibition as a therapeutic strategy for osteoarthritis. The compound serves as a pharmacological intervention to halt the progression of osteoarthritis. |
| Enzyme Assay |
In vitro enzyme or receptor binding (non-cell) assays for CL82198 involve measuring its inhibition of MMP-13 enzymatic activity. The assay uses a purified recombinant MMP-13 enzyme and a fluorogenic peptide substrate. The cleavage of the substrate by MMP-13 releases a fluorescent product. The compound is incubated with the enzyme and substrate at varying concentrations, and the decrease in fluorescence is measured to determine the IC50. For CL82198, an IC50 of approximately 10 μM has been reported. Selectivity is assessed by testing the compound against a panel of other MMPs, such as MMP-1, MMP-9, and TACE.
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| Cell Assay |
In vitro cell-based assays for CL82198 are performed using chondrocytes or other cell types relevant to osteoarthritis. Cells are treated with the compound, and the production and activity of MMP-13 are measured. The degradation of extracellular matrix components, such as collagen type II, is assessed. The compound's effects on cell viability, proliferation, and inflammatory responses are also evaluated. CL82198 significantly reduces the migration of LS174 cells by 55% at 10 uM.
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| Animal Protocol |
Animal/Disease Models: 10weeks old C57BL/6J mice (undergoing MLI surgery) [4]
Doses: 1, 5, 10 mg/kg body weight Route of Administration: intraperitoneal (ip) injection; every other day for 12 weeks Experimental Results: Prevention and mitigation Progression of MLI-induced osteoarthritis. In vivo animal experiments for CL82198 are conducted using mouse models of osteoarthritis, such as the MLI model. The compound is administered intraperitoneally, and its effects on cartilage degeneration, synovial inflammation, and osteophyte formation are assessed. Histological analysis of joint tissues is performed to evaluate the severity of osteoarthritis. The expression of MMP-13 and other markers of cartilage degradation is measured in tissue samples. |
| ADME/Pharmacokinetics |
Pharmacokinetic (PK) properties of CL82198 indicate that it is orally bioavailable. The compound has a molecular weight of 338.83 and a molecular formula of C17H33N2O3·HCl. It is a white solid. The compound is typically administered orally or intraperitoneally in animal studies. Specific PK parameters, such as half-life and bioavailability, are determined in preclinical studies via LC-MS/MS analysis of plasma samples.
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| Toxicity/Toxicokinetics |
Toxicology (toxicology) data for CL82198 are characteristic of a research compound. As a selective MMP-13 inhibitor, its safety profile is an important consideration. The compound is generally well-tolerated at effective doses. The lack of activity against other MMPs, such as MMP-1 and MMP-9, may reduce the risk of side effects associated with broad-spectrum MMP inhibitors, such as musculoskeletal syndrome. However, its long-term safety profile requires further evaluation.
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| References |
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| Additional Infomation |
N-[4-(4-morpholino)butyl]-2-benzofuran carboxamide is a member of the benzofuran class of compounds.
Other information: CL82198 is a research compound used to study the role of MMP-13 in osteoarthritis and other diseases involving cartilage degradation. It is a selective MMP-13 inhibitor that binds to the S1' pocket of the enzyme. The compound is available from chemical suppliers for preclinical research purposes. Its CAS number is 307002-71-7. |
| Molecular Formula |
C17H22N2O3
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|---|---|
| Molecular Weight |
302.374
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| Exact Mass |
302.163
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| CAS # |
307002-71-7
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| Related CAS # |
307002-71-7;1188890-36-9 (HCl);
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| PubChem CID |
2777
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| Appearance |
White to off-white solid powder
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| Boiling Point |
537.1ºC at 760 mmHg
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| Flash Point |
278.6ºC
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| LogP |
3.405
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
22
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| Complexity |
358
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1COCCN1CCCCNC(=O)C2=CC3=CC=CC=C3O2.Cl
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| InChi Key |
KUJQEQAVMNFFAO-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H22N2O3/c20-17(16-13-14-5-1-2-6-15(14)22-16)18-7-3-4-8-19-9-11-21-12-10-19/h1-2,5-6,13H,3-4,7-12H2,(H,18,20)
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| Chemical Name |
N-(4-morpholin-4-ylbutyl)-1-benzofuran-2-carboxamide
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| Synonyms |
CL-82198; CL 82198; CL82198
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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 (~330.72 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (8.27 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 (8.27 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 (8.27 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 | 3.3072 mL | 16.5360 mL | 33.0721 mL | |
| 5 mM | 0.6614 mL | 3.3072 mL | 6.6144 mL | |
| 10 mM | 0.3307 mL | 1.6536 mL | 3.3072 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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