| Identification | Back Directory | [Name]
PXS-4681A | [CAS]
1478364-87-2 | [Synonyms]
PXS-4681
PXS-4681A
(Z)-4-((2-(Aminomethyl)-3-fluoroallyl)oxy)benzenesulfonamide hydrochloride | [Molecular Formula]
C10H14ClFN2O3S | [MOL File]
1478364-87-2.mol | [Molecular Weight]
296.74 |
| Hazard Information | Back Directory | [Uses]
PXS-4681A is a potent, selective, irreversible and orally active semicarbazide-sensitive amine oxidase (SSAO; VAP-1) inhibitor with a Ki of 37 nM. PXS-4681A shows highly selectivity over related amine oxidases, ion channels, and seven-transmembrane domain receptors. PXS-4681A has anti-inflammatory effects[1]. | [Enzyme inhibitor]
This SSAO/VAP-1-directed anti-inflammatory agent (FW = 342.84 g/mol) is a potent and selective mechanism-based inhibitor (Ki = 37 nM; kinact = 0.26 min–1) of Semicarbazide-Sensitive Amine Oxidase (SSAO), or Vascular Adhesion Protein-1 (VAP-1), a copper-dependent amine oxidase associated with various forms of inflammation and fibrosis. SSAO/VAP-1 catalyzes the oxidation of primary amine substrates (including benzylamine, tyramine, methylamine, n-decylamine, histamine, tryptamine or b-phenylethylamine) to aldehydes, releasing ammonia and hydrogen peroxide upon regeneration of its 6-hydroxy-dopa-quinone (TPQ) co-factor. PXS-4681A is highly selective for SSAO/VAP-1, when profiled against related amine oxidases, ion channels and 7-TM receptors, superior to inhibitors reported previously. While the exact physiological role of this enzyme is presently not well understood, PXS-4681A (at 2 mg/kg) attenuates neutrophil migration, TNF-α and IL-6 levels in mouse models of lung inflammation and localized inflammation. Such findings suggest SSAO inhibition leads to decreased neutrophil rolling/extravasation, resulting in a reduction in inflammation. | [in vivo]
PXS-4681A (2 mg/kg; PO; single dose) attenuates neutrophil migration, tumor necrosis factor-α, and interleukin-6 levels in mouse models of lung inflammation and localized inflammation[1].
In rats, PXS-4681A is well absorbed with good bioavailability and oral half-life at the 10 mg/kg i.v. dose and the 20 mg/kg PO dose. Similarly, in BALB/C mice, PXS-4681A is well absorbed with good bioavailability and oral half-life at 2 mg/kg in both intravenous and oral studies[1]. | Animal Model: | Carrageenan-induced skin inflammation mice[1] | | Dosage: | 2 mg/kg
| | Administration: | oral administration; single dose | | Result: | Reduced local inflammation, causing a significant reduction in exudate volume by 25%. |
| [References]
[1] Jonathan S Foot, et al. PXS-4681A, a potent and selective mechanism-based inhibitor of SSAO/VAP-1 with anti-inflammatory effects in vivo. J Pharmacol Exp Ther. 2013 Nov;347(2):365-74. DOI:10.1124/jpet.113.207613 |
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| Company Name: |
Bide Pharmatech Ltd.
|
| Telephone: |
400-1647117 13681763483 |
| Website: |
https://www.bidepharm.com/ |
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