| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| 10mg | |||
| Other Sizes |
| Targets |
MMP-13 0.036 nM (IC50) MMP-2 180 nM (IC50) MMP-3 1100 nM (IC50)
MMP-13 (IC50 = 0.036 nM). It shows excellent selectivity (greater than 1,500-fold) over other MMPs, including MMP-1, -3, -7, -8, -9, -14, and TACE. |
|---|---|
| ln Vitro |
Slices of bovine nasal cartilage that had been cultured for up to 14 days were used in an assay called bovine nasal cartilage (BNC) to investigate the chondrocyte-mediated degradation of cartilage. The in vitro degradation of BNC caused by IL-1 and OSM can be effectively inhibited by MMP13-IN-2 (0.01-1 µM) with respective inhibitions of -17.6%, 48.4%, and 70.8% of cartilage degradation[1].
MMP13-IN-2 is a potent inhibitor of MMP-13 with an IC50 of 0.036 nM and demonstrates over 1,500-fold selectivity for MMP-13 over other MMPs. In a bovine nasal cartilage (BNC) assay, MMP13-IN-2 (0.01-1 uM) effectively prevented IL-1/OSM-induced degradation of cartilage in a dose-dependent manner, with inhibition percentages of -17.6%, 48.4%, and 70.8%, respectively. |
| ln Vivo |
In rats and mice (F% = 33 and 38, respectively), MMP13-IN-2 (oral gavage; 1 mg/kg) exhibits the optimal combination of CYP3A4 inhibition risk and oral exposure[1].
In vivo, MMP13-IN-2 is orally active with excellent bioavailability in rats (F% = 33) and mice (F% = 38) following oral gavage at a dose of 1 mg/kg. It has been shown to block the release of collagen from cartilage and has potential for research into collagenase-related diseases such as osteoarthritis and cancer. |
| Enzyme Assay |
For non-cellular assays, recombinant MMP-13 enzyme is incubated in a standard assay buffer (e.g., 50 mM Tris-HCl, pH 7.5, 10 mM CaCl2, 150 mM NaCl). A fluorogenic peptide substrate (e.g., Mca-PLGL-Dpa-AR-NH2) is added. MMP13-IN-2 is added at varying concentrations (0.001-10 nM). The reaction is monitored by fluorescence (excitation 325 nm, emission 393 nm). The IC50 value is calculated from the dose-response curve.
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| Cell Assay |
For cell-based assays, primary bovine nasal cartilage (BNC) explants are cultured in the presence of IL-1/OSM to induce matrix degradation. MMP13-IN-2 (0.01-1 uM) is added to the culture medium. The release of glycosaminoglycans (GAGs) and collagen into the medium is measured as indicators of cartilage degradation. The inhibition of degradation is calculated by comparing treated explants to untreated controls.
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| Animal Protocol |
For animal studies, MMP13-IN-2 can be administered orally to rodent models of osteoarthritis (OA), e.g., by surgical destabilization of the medial meniscus (DMM) or by chemical induction with MIA. Doses may range from 1-10 mg/kg daily. Efficacy can be assessed by histological scoring of cartilage degradation (e.g., OARSI score), histomorphometry, and by measuring serum biomarkers of cartilage turnover (e.g., CTX-II).
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| ADME/Pharmacokinetics |
MMP13-IN-2 is orally bioavailable. In rats and mice, oral administration (gavage) of 1 mg/kg resulted in an oral bioavailability (F%) of 33% and 38%, respectively. Its half-life, volume of distribution, and clearance are consistent with an orally active small molecule. The compound is soluble in DMSO at 100 mg/mL.
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| Toxicity/Toxicokinetics |
MMP13-IN-2 is a small molecule with a molecular weight of 506.51 g/mol. It has excellent selectivity (>1500-fold) over other MMP family members, which minimizes off-target toxicity. In the BNC explant model, concentrations up to 1 uM were well-tolerated, with no signs of cytotoxicity. As an experimental compound, standard safety precautions for handling research chemicals should be followed.
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| References | |
| Additional Infomation |
MMP13-IN-2 is a highly selective and potent MMP-13 inhibitor. Its favorable oral bioavailability and excellent target selectivity make it a promising drug candidate for osteoarthritis and other collagenase-related diseases. It is a research compound and is not approved for clinical use. It has a molecular formula of C24H19FN6O4S and was disclosed in a 2017 publication by Hiroshi Nara et al. in the Journal of Medicinal Chemistry.
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| Molecular Formula |
C24H19FN6O4S
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|---|---|
| Molecular Weight |
506.51
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| Exact Mass |
506.117
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| CAS # |
935759-55-0
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| PubChem CID |
16719301
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| Appearance |
White to off-white solid powder
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| Density |
1.5±0.1 g/cm3
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| Index of Refraction |
1.727
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| LogP |
2.8
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
36
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| Complexity |
822
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1=CC(=CC(=C1)OCCOC2=NC=NN2)CNC(=O)C3=NC4=C(C(=CS4)C5=CC(=CC=C5)F)C(=O)N3
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| InChi Key |
MLUCCAMJMIYYED-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H19FN6O4S/c25-16-5-2-4-15(10-16)18-12-36-23-19(18)21(32)29-20(30-23)22(33)26-11-14-3-1-6-17(9-14)34-7-8-35-24-27-13-28-31-24/h1-6,9-10,12-13H,7-8,11H2,(H,26,33)(H,27,28,31)(H,29,30,32)
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| Chemical Name |
5-(3-fluorophenyl)-4-oxo-N-[[3-[2-(1H-1,2,4-triazol-5-yloxy)ethoxy]phenyl]methyl]-3H-thieno[2,3-d]pyrimidine-2-carboxamide
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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 (197.43 mM)
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|---|---|
| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.9743 mL | 9.8715 mL | 19.7429 mL | |
| 5 mM | 0.3949 mL | 1.9743 mL | 3.9486 mL | |
| 10 mM | 0.1974 mL | 0.9871 mL | 1.9743 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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