| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
NOX1
NADPH oxidase 1 (NOX1). NoxA1ds is a peptide inhibitor that selectively targets NOX1 by establishing a critical interaction site for Nox1-NOXA1 binding required for enzyme activation, thereby blocking superoxide anion production. |
|---|---|
| ln Vitro |
In vitro, NoxA1ds is a potent and highly selective inhibitor of NOX1, with an IC50 of 20 nM. It displays excellent selectivity for NOX1 over NOX2, NOX4, NOX5, and xanthine oxidase. The peptide works by binding to the NOX1/NOXA1 interface, blocking the protein-protein interaction necessary for enzyme activation.
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| ln Vivo |
NoxA1ds has been used in vivo to study the role of NOX1 in pulmonary hypertension and other diseases. In a pulmonary hypertension model, inhibiting NOX1 with NOXA1ds revealed an antagonistic effect of NOX1 on endothelial TRPV4 channels, which led to increased pulmonary artery pressure. The peptide has also been shown to attenuate VEGF-induced human pulmonary artery endothelial cell migration under hypoxic conditions in vitro.
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| Enzyme Assay |
For non-cellular assays, the activity of NOX1 can be measured in a cell-free system using recombinant NOX1 and its activator proteins (e.g., p67phox, NOXA1) with a substrate such as arachidonic acid. Superoxide production is detected by the reduction of cytochrome c or by luminescence using L-012 or lucigenin. NoxA1ds is added at varying concentrations (1-100 nM), and the IC50 is calculated from the resulting dose-response curve.
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| Cell Assay |
For cell-based assays, NOX1-expressing cells (e.g., HT-29 human colon adenocarcinoma cells) are pre-incubated with NoxA1ds (10-500 nM) for 1-2 hours. NOX1 activity is then stimulated with a phorbol ester (PMA) or other activators. The production of superoxide is measured by a chemiluminescence-based assay using L-012 or by nitroblue tetrazolium (NBT) reduction. The IC50 value for the inhibition of NOX1-derived O2- production is calculated.
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| Animal Protocol |
For animal studies, NoxA1ds can be administered via aerosolization, intraperitoneally (IP), or intravenously (IV) to rodent models of pulmonary hypertension, atherosclerosis, or other diseases. Doses are typically in the range of 0.1-1 mg/kg. The peptide is often delivered by intratracheal instillation or nebulization for pulmonary studies. Efficacy endpoints include measures of pulmonary artery pressure (by right heart catheterization), reactive oxygen species (ROS) levels in lung tissue, and histological analysis of vascular remodeling.
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| ADME/Pharmacokinetics |
NoxA1ds is an 11-amino acid peptide (sequence: EPVDALGKAKV) with a molecular weight of approximately 1239.3 g/mol. It is cell-permeable, which is a key feature for its activity, as it must reach the intracellular NOX1/NOXA1 complex. It is typically stored as a lyophilized powder at -20degC and reconstituted in a buffer such as PBS or a small amount of DMSO before use.
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| Toxicity/Toxicokinetics |
NoxA1ds has been reported to have a lower risk of side effects and toxicity when used in vivo compared to other inhibitors. In the University of Pittsburgh invention report, it is stated that the peptide selectively inhibits Nox1 activity with a lower risk of side effects and toxicity. Studies using NoxA1ds in concentrations up to 10 mM have shown no inhibition of NOX2 or Xanthine Oxidase, confirming the selective nature of this inhibitor.
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| References | |
| Additional Infomation |
NoxA1ds is the first reported specific peptide inhibitor of NADPH Oxidase 1 (NOX1). It was developed by researchers at the University of Pittsburgh. The peptide is a valuable tool for studying NOX1 biology, which is involved in hypertension, atherosclerosis, cancer, and various inflammatory conditions. The compound is not an approved drug and is intended for research use only. It is often supplied as a TFA salt.
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| Molecular Formula |
C50H88N14O15
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|---|---|
| Molecular Weight |
1125.31853199005
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| Exact Mass |
1124.655
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| CAS # |
1435893-78-9
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| Related CAS # |
NoxA1ds TFA
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| PubChem CID |
121513898
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| Appearance |
White to off-white solid powder
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| LogP |
-7.2
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| Hydrogen Bond Donor Count |
15
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| Hydrogen Bond Acceptor Count |
18
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| Rotatable Bond Count |
37
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| Heavy Atom Count |
79
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| Complexity |
2130
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| Defined Atom Stereocenter Count |
10
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| SMILES |
O=C([C@@H]1CCCN1C([C@H](CCC(=O)O)N)=O)N[C@H](C(N[C@H](C(N[C@@H](C)C(N[C@H](C(NCC(N[C@H](C(N[C@@H](C)C(N[C@H](C(N[C@H](C(N)=O)C(C)C)=O)CCCCN)=O)=O)CCCCN)=O)=O)CC(C)C)=O)=O)CC(=O)O)=O)C(C)C
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| InChi Key |
DHBOJLLJKHKZGT-XTGVMIFDSA-N
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| InChi Code |
InChI=1S/C50H88N14O15/c1-25(2)22-33(44(73)55-24-36(65)58-31(14-9-11-19-51)45(74)56-28(7)42(71)59-32(15-10-12-20-52)46(75)62-39(26(3)4)41(54)70)60-43(72)29(8)57-47(76)34(23-38(68)69)61-49(78)40(27(5)6)63-48(77)35-16-13-21-64(35)50(79)30(53)17-18-37(66)67/h25-35,39-40H,9-24,51-53H2,1-8H3,(H2,54,70)(H,55,73)(H,56,74)(H,57,76)(H,58,65)(H,59,71)(H,60,72)(H,61,78)(H,62,75)(H,63,77)(H,66,67)(H,68,69)/t28-,29-,30-,31-,32-,33-,34-,35-,39-,40-/m0/s1
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| Chemical Name |
(4S)-4-amino-5-[(2S)-2-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[(2S)-1-[[2-[[(2S)-6-amino-1-[[(2S)-1-[[(2S)-6-amino-1-[[(2S)-1-amino-3-methyl-1-oxobutan-2-yl]amino]-1-oxohexan-2-yl]amino]-1-oxopropan-2-yl]amino]-1-oxohexan-2-yl]amino]-2-oxoethyl]amino]-4-methyl-1-oxopentan-2-yl]amino]-1-oxopropan-2-yl]amino]-3-carboxy-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamoyl]pyrrolidin-1-yl]-5-oxopentanoic acid
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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, avoid exposure to moisture. |
| 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) |
H2O: 100 mg/mL (88.86 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 100 mg/mL (88.86 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with sonication.
(Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 0.8886 mL | 4.4432 mL | 8.8864 mL | |
| 5 mM | 0.1777 mL | 0.8886 mL | 1.7773 mL | |
| 10 mM | 0.0889 mL | 0.4443 mL | 0.8886 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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