Home
Resources
Publications
PXS-4681A, a Potent and Selective Mechanism-Based Inhibitor of SSAO/VAP-1 With Anti-Inflammatory Effects in Vivo

PXS-4681A, a Potent and Selective Mechanism-Based Inhibitor of SSAO/VAP-1 With Anti-Inflammatory Effects in Vivo

Jonathan S Foot, Tin T Yow, Heidi Schilter, Alberto Buson, Mandar Deodhar, Alison D Findlay, Lily Guo, Ian A McDonald, Craig I Turner, Wenbin Zhou, Wolfgang Jarolimek

J Pharmacol Exp Ther. 2013 Nov;347(2):365-74.

PMID: 23943052

Abstract:

Semicarbazide-sensitive amine oxidase (SSAO), also known as vascular adhesion protein-1 (VAP-1), is a member of the copper-dependent amine oxidase family that is associated with various forms of inflammation and fibrosis. To investigate the therapeutic potential of SSAO/VAP-1 inhibition, potent and selective inhibitors with drug-like properties are required. PXS-4681A [(Z)-4-(2-(aminomethyl)-3-fluoroallyloxy)benzenesulfonamide hydrochloride] is a mechanism-based inhibitor of enzyme function with a pharmacokinetic and pharmacodynamic profile that ensures complete, long-lasting inhibition of the enzyme after a single low dose in vivo. PXS-4681A irreversibly inhibits the enzyme with an apparent Ki of 37 nM and a kinact of 0.26 min(-1) with no observed turnover in vitro. It is highly selective for SSAO/VAP-1 when profiled against related amine oxidases, ion channels, and seven-transmembrane domain receptors, and is superior to previously reported inhibitors. In mouse models of lung inflammation and localized inflammation, dosing of this molecule at 2 mg/kg attenuates neutrophil migration, tumor necrosis factor-α, and interleukin-6 levels. These results demonstrate the drug-like properties of PXS-4681A and its potential use in the treatment of inflammation.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP1158976261	PXS-4681A hydrochloride		1158976-26-1	Price

As a specialist in analytical chemical Products, Alfa Chemistry offers consumers a wealth of raw materials and a full range of technologies and services.

QUICK LINKS

HEADQUARTERS

Tel:

Fax:

Email: