| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
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| 10mg |
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| 50mg |
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| 100mg |
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| Other Sizes |
| Targets |
Matrix Metalloproteinase-2 (MMP-2, Gelatinase A) (IC50 = 12 nM) [1]
Matrix Metalloproteinase-9 (MMP-9, Gelatinase B) (IC50 = 200 nM) [1] Matrix Metalloproteinase-1 (MMP-1) (IC50 > 50,000 nM) [1] Matrix Metalloproteinase-3 (MMP-3) (IC50 = 4500 nM) [1] Matrix Metalloproteinase-7 (MMP-7) (IC50 > 50,000 nM) [1] |
|---|---|
| ln Vitro |
ARP-100 (50 nM) exhibits a notable decrease in the overall quantity of invasive elongations [1].
ARP100 (referred to as compound 10a in the study) was tested for its inhibitory activity against a panel of matrix metalloproteinases (MMP-1, -2, -3, -7, and -9). It demonstrated potent inhibition of MMP-2 with an IC50 of 12 nM. It showed moderate inhibition of MMP-9 (IC50 = 200 nM) and MMP-3 (IC50 = 4500 nM), and was practically inactive against MMP-1 and MMP-7, with IC50 values greater than 50,000 nM. [1] The selectivity of ARP100 for MMP-2 over other MMPs was calculated. The selectivity ratios were >4000 for MMP-1/MMP-2, 375 for MMP-3/MMP-2, >4000 for MMP-7/MMP-2, and 17 for MMP-9/MMP-2. This indicates that ARP100 is a highly selective inhibitor of MMP-2. [1] In an in vitro model of invasion using matrigel, ARP100 at a concentration of 50 nM significantly reduced the invasive behavior of HT1080 fibrosarcoma cells, which over-express MMP-2 and MMP-9. The number of invasive cellular elongations was markedly lower compared to untreated controls. [1] |
| Enzyme Assay |
The inhibitory activity of ARP100 against various MMPs was determined using a fluorimetric assay. Proenzymes (pro-MMP-1, -2, -3, -7, -9) were activated prior to use. Pro-MMP-1 was activated with 2 mM APMA for 1 hour at 37°C. Pro-MMP-2 and pro-MMP-7 were activated with 2 mM APMA for 1 hour at 25°C. Pro-MMP-9 was activated with 1 mM APMA for 1 hour at 37°C. Pro-MMP-3 was activated with trypsin (13 μg/mL) for 15 minutes at 37°C, followed by the addition of soybean trypsin inhibitor (50 μg/mL). The activated enzyme was incubated with seven different concentrations of ARP100 (ranging from 1 to 1500 nM, depending on the MMP) in assay buffer (50 mM Tris-HCl, pH 7.5, 150 mM NaCl, 10 mM CaCl₂, 0.05% Brij 35, 1% DMSO) for 4 hours at 25°C. The fluorogenic substrate Mca-Pro-Leu-Gly-Leu-Dpa-Ala-Arg-NH₂ was then added to a final concentration of 1 μM. The increase in fluorescence (λex = 328 nm, λem = 393 nm) was continuously recorded. Percent inhibition was calculated relative to control reactions without inhibitor, and IC50 values were determined by fitting the data to the equation Vᵢ/V₀ = 1/(1+[I]/IC₅₀). [1]
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| Cell Assay |
The anti-invasive properties of ARP100 were evaluated using a Matrigel invasion assay with HT1080 human fibrosarcoma cells. Matrigel, a basement membrane extract, was diluted to 14 mg/mL and 0.3 mL was pipetted into each well of a 24-well plate and allowed to polymerize at 37°C for 1 hour. HT1080 cells (5 x 10⁴ cells) were seeded onto the matrigel layer in 1 mL of complete medium and treated with 50 nM of ARP100. Control cells were treated with the carrier (DMSO) alone. The plates were incubated at 37°C in a 5% CO₂ humidified atmosphere for 24 hours and then photographed. The formation of invasive structures (cellular elongations protruding from cell colonies) was qualitatively assessed. Treatment with ARP100 resulted in a marked reduction in the number of these invasive structures compared to controls, indicating similar anti-invasive properties to the reference drug CGS27023A. [1]
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| References |
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| Additional Infomation |
ARP100 (compound 10a) is a new N-aryl sulfonyl-N-alkoxyaminoacetohydrazonic acid derivative. It was designed as an "oxa-analogue" of known sulfonamide-based MMP inhibitors, where the methylenic carbon of the isobutyl group is replaced by an oxygen atom, and it incorporates a biphenylsulfonamide group. [1]
The combination of the oxyanamic oxygen and the biphenyl group in ARP100 is believed to contribute to its high selectivity for MMP-2 over MMP-1. This is likely due to the ability of the biphenyl group to fit into the long, rectilinear S1' pocket of MMP-2, while the oxyanamic oxygen may act as a hydrogen bond acceptor, strengthening interactions with the enzyme's active site. [1] ARP100 exhibits a high selectivity profile for MMP-2, with an MMP-1/MMP-2 selectivity ratio greater than 4000. This is significantly more selective than the reference compounds CGS27023A (ratio 2.8) and AG-3340 (ratio 99). Its lack of activity against MMP-1 is considered important, as inhibition of MMP-1 is thought to be linked to the musculoskeletal side effects seen with non-selective MMP inhibitors. [1] |
| Molecular Formula |
C17H20N2O5S
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|---|---|
| Molecular Weight |
364.416
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| Exact Mass |
364.109
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| CAS # |
704888-90-4
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| PubChem CID |
10044321
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| Appearance |
Off-white to light yellow solid powder
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| Density |
1.3±0.1 g/cm3
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| Index of Refraction |
1.589
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| LogP |
2.08
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
25
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| Complexity |
518
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
PHGLPDURIUEELR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C17H20N2O5S/c1-13(2)24-19(12-17(20)18-21)25(22,23)16-10-8-15(9-11-16)14-6-4-3-5-7-14/h3-11,13,21H,12H2,1-2H3,(H,18,20)
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| Chemical Name |
N-hydroxy-2-[(4-phenylphenyl)sulfonyl-propan-2-yloxyamino]acetamide
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| Synonyms |
ARP100 ARP 100 ARP-100
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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 (~274.41 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.86 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 (6.86 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. 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 (6.86 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 | 2.7441 mL | 13.7204 mL | 27.4409 mL | |
| 5 mM | 0.5488 mL | 2.7441 mL | 5.4882 mL | |
| 10 mM | 0.2744 mL | 1.3720 mL | 2.7441 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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