PXS-4728A free base
Based on 2 publication(s) in Google Scholar
PXS-4728A free base is an orally active, selective VAP-1/SSAO inhibitor with an IC50 of 5 nM and a Ki of 175 nM. PXS-4728A free base 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 free base reduces the formation and progression of atherosclerotic plaques, and decreases blood lipid and blood glucose levels as well as body weight gain. PXS-4728A free base 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.
- CAS No.: 1478364-40-7
- Formula: C15H21FN2O2
- Molecular Weight:280.34
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Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
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Biological Activity
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Chemical Information
- Purity & Documentation
- References
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Publications Citing Use of MedChemExpress (MCE) PXS-4728A free base
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Biological Activity
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MMP-9 |
PXS-4728A free base 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 free base 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 free base 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 free base (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 free base (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 free base (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 free base (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 free base (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.
Chemical Information
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CAS No. 1478364-40-7
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Molecular Weight 280.34
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Formula C15H21FN2O2
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SMILES
CC(C)(C)NC(C1=CC=C(C=C1)OC/C(CN)=C/F)=O
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Synonyms
BI-1467335 free base
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Shipping
Room temperature in continental US; may vary elsewhere.
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Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
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
Purity & Documentation
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]
Calculators
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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