PXS-4728A
Based on 2 publication(s) in Google Scholar
PXS-4728A is an orally active, selective VAP-1/SSAO inhibitor with an IC50 of 5 nM and a Ki of 175 nM. PXS-4728A inhibits the expression of MMP-9. It reduces cell rolling, adhesion and migration, decreases cell infiltration levels, pro-inflammatory cytokines, chemokines and collagen deposition, and improves pulmonary function. PXS-4728A reduces the formation and progression of atherosclerotic plaques, and decreases blood lipid and blood glucose levels as well as body weight gain. PXS-4728A can be used in research related to chronic obstructive pulmonary disease, cystic fibrosis, acute pulmonary inflammation, acute lung injury, bronchiolitis obliterans syndrome, rhinovirus-exacerbated asthma, sepsis, Klebsiella pneumoniae pulmonary infection and atherosclerosis.
For research use only. We do not sell to patients.
- Purity: 98.79%
- CAS No.: 1478364-68-9
- Formula: C15H22ClFN2O2
- Molecular Weight:316.80
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Storage:
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
To place orders, for customer services and technical support, please contact: MedChemExpress USA
Tel: 609-228-6898 E-mail: [email protected] [email protected]
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Biological Activity
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Chemical Information
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Solvent & Solubility
- Purity & Documentation
- References
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Help & FAQs
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Publications Citing Use of MedChemExpress (MCE) PXS-4728A
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Biological Activity
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MMP-9 |
PXS-4728A potently inhibits recombinant human VAP-1/SSAO with an IC50 of 5 nM and acts as a mechanism-based inhibitor with a Ki of 175 nM and Kinact of 0.68 min-1[1].
PXS-4728A shows >500-fold selectivity for VAP-1/SSAO over all tested related human amine oxidases, with IC50 values ranging from 2.7 μM to >100 μM for off-target enzymes[1].
PXS-4728A potently inhibits VAP-1/SSAO activity in gonadal fat tissue homogenates from mice, rats, dogs, and rabbits with an IC50 of <10 nM[1].
PXS-4728A (100 μM) does not induce cell toxicity or phospholipidosis in HepG2 cells at concentrations up to 100 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
PXS-4728A (0.2-2 mg/kg; p.o.; single dose) dose-dependently reduces LPS-induced neutrophilic acute lung inflammation in BALB/c mice, with 2 mg/kg achieving a near-complete reduction in BALF neutrophils[1].
PXS-4728A (2 mg/kg; i.p.; single dose) reduces neutrophilic inflammation and airway hyperreactivity in BALB/c mice with rhinovirus-exacerbated allergic asthma[1].
PXS-4728A (2-20 mg/kg; p.o.; daily; 4 days) potently inhibits lung and peripheral SSAO activity, reduces airway inflammatory cell influx, and lowers pro-inflammatory mediator levels in mice with acute cigarette smoke-induced COPD-like inflammation[2].
PXS-4728A (1-10 mg/kg/day; p.o.; daily; 4-12 weeks) reduces atherosclerotic plaque area by 37.59% in cholesterol-fed New Zealand White rabbits, alongside inhibiting SSAO activity, lowering plasma lipids and glucose, and suppressing inflammatory, macrophage, and smooth muscle cell-mediated atherogenic pathways[4].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
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Animal Model:C57BL/6 (female, 6-8 weeks old, acute cigarette smoke-induced model)[2]
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Dosage:2 mg/kg; 6 mg/kg; 12 mg/kg; 20 mg/kg
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Administration:p.o.; daily; 4 days
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Result:Completely inhibited constitutive lung SSAO activity at 2, 6, and 20 mg/kg.
Completely inhibited SSAO activity in inguinal fat at 20 mg/kg.
Reduced total leukocyte numbers in bronchoalveolar lavage fluid (BALF) at 12 and 20 mg/kg.
Reduced macrophage and lymphocyte counts in BALF at 12 mg/kg.
Suppressed neutrophil counts in BALF at 20 mg/kg.
Reduced BALF CXCL1 levels at 12 and 20 mg/kg.
Reduced BALF TNFα levels back to baseline at 20 mg/kg.
Reduced BALF TNFα levels in a dose-dependent manner at 12 mg/kg.
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Animal Model:New Zealand White rabbits (male, 2 kg weight, atherosclerosis model via 0.5% cholesterol-enriched diet for 12 weeks)[4]
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Dosage:1 mg/kg/day (dose-finding, 4 days); 10 mg/kg/day (dose-finding, 4 days); 10 mg/kg/day (12 weeks)
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Administration:p.o.; daily; 4 consecutive days (dose-finding); p.o.; daily; 12 weeks
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Result:Inhibited SSAO activity by 80% at 1 mg/kg/day for 4 days in abdominal fat.
Inhibited SSAO activity by >90% at 10 mg/kg/day for 4 days in abdominal fat.
Significantly inhibited SSAO-specific hydrogen peroxide production in thoracic aorta, lung, and epididymal fat at 10 mg/kg/day for 12 weeks relative to cholesterol-fed controls.
Reduced body weight to 3.28 kg vs. 3.58 kg in cholesterol-fed controls.
Reduced plasma total cholesterol to 508.4 mg/dl vs. 695.9 mg/dl in cholesterol-fed controls.
Reduced LDL-cholesterol to 403.2 mg/dl vs. 576.8 mg/dl in cholesterol-fed controls.
Reduced glucose to 195.3 mg/dl vs. 258.7 mg/dl in cholesterol-fed controls.
Reduced AST to 209.2 U/l vs. 502.8 U/l in cholesterol-fed controls.
Reduced atherosclerotic plaque area by 37.59% (30.72% of vessel area vs. 68.31% in cholesterol-fed controls).
Significantly decreased intima/media area ratio to 0.29 vs. 0.91 in cholesterol-fed controls.
Reduced aortic wall thickness to 1.22-fold of control vs. 2.12-fold in cholesterol-fed controls.
Significantly reduced aortic expression of adhesion molecules (ICAM-1, VCAM-1, E-selectin), pro-inflammatory cytokines (COX-2, IL-6, MCP-1), macrophage activation markers (RAGE, LOX-1, CD36, TLR-4), macrophage recruitment, MMP-9 expression, smooth muscle cell accumulation in intima, and PCNA-positive proliferating cells relative to cholesterol-fed controls.
| NCT Number | Sponsor | Condition | Start Date |
Phase
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|---|---|---|---|---|
| NCT01329991 | Plexxikon| | 2011-05 | PHASE1 |
Chemical Information
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CAS No. 1478364-68-9
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Appearance Solid
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Molecular Weight 316.80
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Formula C15H22ClFN2O2
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Color White to yellow
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SMILES
O=C(NC(C)(C)C)C1=CC=C(OC/C(CN)=C/F)C=C1.Cl
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Synonyms
BI-1467335
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
4°C, sealed storage, away from moisture
* In solvent : -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture)
Publications (2)
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Journal Impact Factor
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Most Recent
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Nat Commun
Rational design of potent small-molecule SMARCA2/A4 degraders acting via the recruitment of FBXO22. [Abstract]2025 Nov 3;16(1):9679. PMID: 41184243 -
Exp Mol Med
2026 Apr;58(4):1284-1296. PMID: 42009953
Solvent & Solubility
DMSO : 233.33 mg/mL (736.52 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
H2O : 100 mg/mL (315.66 mM; Need ultrasonic)
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
Select the appropriate dissolution method based on your experimental animal and administration route.
- For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
- To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for In Vivo experiments, it is recommended to prepare freshly and use it on the same day.
- The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.08 mg/mL (6.57 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.08 mg/mL (6.57 mM); Clear solution
This protocol yields a clear solution of ≥ 2.08 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (20.8 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
For the following dissolution methods, please prepare the working solution directly:
It is recommended to prepare fresh solutions and use them promptly within a short period of time.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.
Add each solvent one by one: PBS
Solubility: 25 mg/mL (78.91 mM); Clear solution; Need ultrasonic and warming
Please enter the basic information of animal experiments:
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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Working solution concentration: 0.22 mg/mL
This product has good water solubility, please refer to the measured solubility data in water/PBS/Saline for details.
Purity & Documentation
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Data Sheet (281 KB)
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SDS (557 KB)
- English - EN (557 KB)
- Français - FR (557 KB)
- Deutsch - DE (557 KB)
- Norwegian - NO (557 KB)
- Español - ES (557 KB)
- Swedish - SV (557 KB)
- Italian - IT (557 KB)
- Korean - KR (557 KB)
- Portuguese - PT (557 KB)
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Handling Instructions (2659 KB)
References
[1]. Schilter HC, et al. Effects of an anti-inflammatory VAP-1/SSAO inhibitor, PXS-4728A, on pulmonary neutrophil migration. Respiratory research. 2015 Mar 20;16(1):42. [Content Brief]
[2]. Jarnicki AG, et al. The inhibitor of semicarbazide-sensitive amine oxidase, PXS-4728A, ameliorates key features of chronic obstructive pulmonary disease in a mouse model. British journal of pharmacology. 2016 Nov;173(22):3161-3175. [Content Brief]
[3]. Li H, et al. Vascular Adhesion Protein-1 (VAP-1)/Semicarbazide-Sensitive Amine Oxidase (SSAO): A Potential Therapeutic Target for Atherosclerotic Cardiovascular Diseases. Frontiers in pharmacology. 2021;12:679707. [Content Brief]
[4]. Wang SH, et al. Inhibition of Semicarbazide-sensitive Amine Oxidase Reduces Atherosclerosis in Cholesterol-fed New Zealand White Rabbits. Scientific reports. 2018 Jun 18;8(1):9249. [Content Brief]
Complete Stock Solution Preparation Table
Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month (sealed storage, away from moisture). When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| H2O / DMSO | 1 mM | 3.1566 mL | 15.7828 mL | 31.5657 mL | 78.9141 mL |
| 5 mM | 0.6313 mL | 3.1566 mL | 6.3131 mL | 15.7828 mL | |
| 10 mM | 0.3157 mL | 1.5783 mL | 3.1566 mL | 7.8914 mL | |
| 15 mM | 0.2104 mL | 1.0522 mL | 2.1044 mL | 5.2609 mL | |
| 20 mM | 0.1578 mL | 0.7891 mL | 1.5783 mL | 3.9457 mL | |
| 25 mM | 0.1263 mL | 0.6313 mL | 1.2626 mL | 3.1566 mL | |
| 30 mM | 0.1052 mL | 0.5261 mL | 1.0522 mL | 2.6305 mL | |
| 40 mM | 0.0789 mL | 0.3946 mL | 0.7891 mL | 1.9729 mL | |
| 50 mM | 0.0631 mL | 0.3157 mL | 0.6313 mL | 1.5783 mL | |
| 60 mM | 0.0526 mL | 0.2630 mL | 0.5261 mL | 1.3152 mL | |
| 80 mM | 0.0395 mL | 0.1973 mL | 0.3946 mL | 0.9864 mL | |
| 100 mM | 0.0316 mL | 0.1578 mL | 0.3157 mL | 0.7891 mL |
* Note: If you choose water as the stock solution, please dilute it to the working solution, then filter and sterilize it with a 0.22 μm filter before use.
PXS-4728A Related Classifications
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