2. Immunology/Inflammation Metabolic Enzyme/Protease
  3. VAP-1 MMP
  4. PXS-4728A free base

PXS-4728A free base  (Synonyms: BI-1467335 free base)

Cat. No.: HY-112726A
Handling Instructions Technical Support

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.

PXS-4728A free base

PXS-4728A free base Chemical Structure

CAS No. : 1478364-40-7

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PXS-4728A free base Related Antibodies

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1 Publications Citing Use of MCE PXS-4728A free base

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MMP-1 MMP-2 MMP-3 MMP-8 MMP-9 MMP-13 MMP-14 MMP-17 ADAM10 ADAM17 MMP-7 MMP-12 MMP-10 MMP ADAM8 MMP-19

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Description

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[1][2][3][4].

IC50 & Target[4]

MMP-9

 

In Vitro

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 Related Antibodies
Parmacokinetics
Species Dose Route Bioavailability Cmax Clearance (CL) T1/2
Rat[1] 6 mg/kg p.o. 55 % 0.72 μg/mL 45 mL/min/kg /
Rat[1] 3 mg/kg i.v. / 4.21 μg/mL 23 mL/min/kg 1.1 h
Mice[1] 10 mg/kg p.o. 92 % 1.38 μg/mL 98 mL/min/kg /
Mice[1] 5 mg/kg i.v. / 1.6 μg/mL 80 mL/min/kg 0.6 h
In Vivo

PXS-4728A free base (6 mg/kg; p.o.; single dose) completely inhibits CXCL1/KC-induced leukocyte rolling and adhesion in BALB/c mouse cremaster muscle venules[1].
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.

Animal Model: C57BL/6 (female, 6-8 weeks old, acute cigarette smoke-induced model)[2]
Dosage: 2 mg/kg; 6 mg/kg; 12 mg/kg; 20 mg/kg
Administration: p.o.; daily; 4 days
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.
Animal Model: New Zealand White rabbits (male, 2 kg weight, atherosclerosis model via 0.5% cholesterol-enriched diet for 12 weeks)[4]
Dosage: 1 mg/kg/day (dose-finding, 4 days); 10 mg/kg/day (dose-finding, 4 days); 10 mg/kg/day (12 weeks)
Administration: p.o.; daily; 4 consecutive days (dose-finding); p.o.; daily; 12 weeks
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.
Molecular Weight

280.34

Formula

C15H21FN2O2
CAS No.
SMILES

CC(C)(C)NC(C1=CC=C(C=C1)OC/C(CN)=C/F)=O
Shipping

Room temperature in continental US; may vary elsewhere.
Storage

Please store the product under the recommended conditions in the Certificate of Analysis.
Purity & Documentation
References
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PXS-4728A free base Related Classifications

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Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

PXS-4728A1478364-40-7BI-1467335BI1467335BI 1467335VAP-1MMPVascular adhesion protein-1 (VAP-1)Semicarbazide-sensitive amine oxidase (SSAO)Amine oxidase copper-containing 3 (AOC3)Matrix metalloproteinasesoxidative stressKlebsiella pneumoniaeatherosclerosischronic obstructive pulmonary diseaseApoE-/- miceVAP-1/SSAOendothelial dysfunctionleukocyte traffickingNew Zealand White rabbitsHepG2 cellsInhibitorinhibitorinhibit

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