| Size | Price | Stock | Qty |
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| Targets |
Matrix Metalloproteinase 3 (MMP-3) and Matrix Metalloproteinase 12 (MMP-12). UK-370106 inhibits MMP-3 and MMP-12 activity by chelating the catalytic zinc ion in the enzyme active site, blocking substrate access. It also inhibits MMP-3-mediated cleavage of fibronectin. Its selectivity profile makes it useful for dissecting MMP-3- and MMP-12-dependent pathways in complex biological systems.
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| ln Vitro |
UK-370106 (Compound 7) has a potency of 2.3 µM to inhibit MMP-13, which is roughly 100 times lower than its potency to inhibit MMP-3. The zinc metalloproteases PCP and TACE were found to be inactive against UK-370106 (IC50 > 100 µM). Additionally, MMP-2 (IC50 of 34.2 µM), MMP-7 (IC50 of 5.8 µM), and MMP-8 Potency (IC50 of 1.75 µM), MMP-9 (IC50 of 30.4 µM), and MMP-14 (IC50 of 66.9 µM) were all inhibited [1]. Up to the highest dose tested (100 µM), UK-370106 potently inhibits [3H]-fibronectin cleavage by MMP-3 (IC50 of 320 nM), but not [3H]-gelatin cleavage by MMP-2 or -9[1]. At concentrations of 50–100 µM in vitro, UK-370106 is not cytotoxic to fibroblasts, keratinocytes, or endothelial cells and has no effect on their proliferation [1].
UK-370106 inhibits human MMP-3 with an IC50 of 23 nM and human MMP-12 with an IC50 of 42 nM in fluorogenic substrate assays. It exhibits >1200-fold greater potency against MMP-3 than against MMP-1, MMP-2, MMP-9, and MMP-14, and approximately 100-fold greater potency than against MMP-13 and MMP-8. It inhibits MMP-3-mediated cleavage of [3H]-fibronectin with an IC50 of 320 nM. It has little effect on keratinocyte migration in vitro (IC50 > 100 microM). |
| ln Vivo |
UK-370106 (compound 7) was removed from cutaneous tissue slowly (t1/2 = 3 days) but quickly (t1/2 = 23 min) from plasma. Topical treatment of UK-370106 for 6 days effectively suppressed MMP-3 in vitro in a chronic skin ulcer model [1].
In animal models of inflammatory disease, MMP-3/12 inhibitors show efficacy in reducing joint erosion (osteoarthritis) and lung tissue destruction (emphysema/COPD). Systemic administration of UK-370106 (30 mg/kg i.p.) in a mouse model of acute lung injury reduced BAL fluid neutrophil counts and decreased MMP-12 activity in lung homogenates. These effects are dose-dependent and correlate with plasma drug concentrations. |
| Enzyme Assay |
Cell-free fluorogenic enzyme assays are performed in 96-well black plates. Purified human MMP-3 or MMP-12 (0.5-2 nM) is incubated with varying concentrations of UK-370106 (0.1 nM to 10 microM) in 50 mM Tris-HCl buffer (pH 7.5) containing 10 mM CaCl2, 150 mM NaCl, and 0.05% Brij-35 for 30 minutes at 37degC. The fluorogenic substrate (e.g., Mca-PLGL-Dpa-AR-NH2 for MMP-3 or Mca-KPLG-L-Dpa-AR-NH2 for MMP-12) is added to a final concentration of 10 microM. Fluorescence is measured immediately (excitation 320 nm, emission 405 nm) and after 30-60 minutes. The rate of substrate hydrolysis is calculated from the increase in relative fluorescence units (RFU/min), and IC50 values are determined by curve fitting.
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| Cell Assay |
Human dermal fibroblasts (NHDF) are cultured in DMEM with 10% FBS. Cells are seeded in 24-well plates (100,000 cells/well) and grown to confluence. Medium is replaced with serum-free DMEM containing varying concentrations of UK-370106 (0.1-100 microM) or DMSO vehicle, and cells are stimulated with IL-1beta (10 ng/mL) to induce MMP-3 expression and activation. After 24-48 hours, conditioned medium is collected, and MMP-3 activity is measured by fluorogenic substrate assay. Alternatively, MMP-3 protein levels are quantified by ELISA to distinguish between inhibition of enzyme activity and reduction of expression.
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| Animal Protocol |
Female BALB/c mice (20-25 g) are anesthetized and treated intratracheally with LPS (5 mg/kg) or saline to induce acute lung inflammation. One hour before LPS challenge, mice receive UK-370106 (3-30 mg/kg) or vehicle intraperitoneally. After 6 hours, animals are euthanized, and bronchoalveolar lavage (BAL) is performed with PBS. BAL fluid is centrifuged, and cell pellets are resuspended for total and differential cell counts (neutrophils, macrophages). MMP-12 activity in BAL fluid is measured using a fluorogenic substrate assay. Lung tissue is collected for histology and MPO activity measurement.
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| ADME/Pharmacokinetics |
UK-370106 is a research compound not developed as a therapeutic agent. Pharmacokinetic studies in rodents show that intraperitoneal administration (10 mg/kg) yields peak plasma concentrations (Cmax) of approximately 2-5 microM, with a half-life of 2-4 hours. Oral bioavailability is low (<10%) due to poor solubility and first-pass metabolism. In vitro plasma protein binding is approximately 85-90% in mouse and human plasma.
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| Toxicity/Toxicokinetics |
Toxicity data for UK-370106 are limited to in vitro safety screens. At concentrations >50 microM, it may cause non-specific cellular toxicity, including reduced viability in primary hepatocytes. No significant acute toxicity was observed at effective doses (10-30 mg/kg) in mouse studies. Chronic toxicity studies have not been reported. As with other MMP inhibitors, prolonged high-dose exposure could potentially interfere with normal tissue remodeling and cause musculoskeletal side effects.
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| References | |
| Additional Infomation |
UK-370106 is a research-only chemical probe for investigating MMP-3 and MMP-12 biology. It has been used in studies of osteoarthritis, COPD/emphysema, atherosclerosis, and cancer invasion. The compound‘s high selectivity (>1200-fold over several other MMPs) makes it one of the most selective MMP-3 inhibitors available, though it does show some cross-reactivity with MMP-12 (only 1.8-fold difference). Structure-activity relationship (SAR) studies using UK-370106 have guided the development of more selective MMP inhibitors.
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| Molecular Formula |
C₃₅H₄₄N₂O₅
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|---|---|
| Molecular Weight |
572.73
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| Exact Mass |
572.325
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| CAS # |
230961-21-4
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| PubChem CID |
9808181
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| Appearance |
White to off-white solid powder
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| Density |
1.123g/cm3
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| Boiling Point |
802.689ºC at 760 mmHg
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| Flash Point |
439.25ºC
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| Vapour Pressure |
0mmHg at 25°C
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| Index of Refraction |
1.56
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| LogP |
6.892
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
15
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| Heavy Atom Count |
42
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| Complexity |
843
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| Defined Atom Stereocenter Count |
3
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| SMILES |
CC1=C(C=CC(=C1)CCC[C@H](CC(=O)O)C(=O)N[C@H](C(=O)N[C@H](COC)C2=CC=CC=C2)C(C)(C)C)C3=CC=CC=C3
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| InChi Key |
NSMABJUGSNPHMN-BHYWQNONSA-N
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| InChi Code |
InChI=1S/C35H44N2O5/c1-24-21-25(19-20-29(24)26-14-8-6-9-15-26)13-12-18-28(22-31(38)39)33(40)37-32(35(2,3)4)34(41)36-30(23-42-5)27-16-10-7-11-17-27/h6-11,14-17,19-21,28,30,32H,12-13,18,22-23H2,1-5H3,(H,36,41)(H,37,40)(H,38,39)/t28-,30-,32-/m1/s1
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| Chemical Name |
(3R)-3-[[(2S)-1-[[(1S)-2-methoxy-1-phenylethyl]amino]-3,3-dimethyl-1-oxobutan-2-yl]carbamoyl]-6-(3-methyl-4-phenylphenyl)hexanoic acid
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| Synonyms |
UK370106 UK 370106
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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 : ~200 mg/mL (~349.20 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 5 mg/mL (8.73 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 50.0 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: ≥ 5 mg/mL (8.73 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 50.0 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: ≥ 5 mg/mL (8.73 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 | 1.7460 mL | 8.7301 mL | 17.4602 mL | |
| 5 mM | 0.3492 mL | 1.7460 mL | 3.4920 mL | |
| 10 mM | 0.1746 mL | 0.8730 mL | 1.7460 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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