Overview
- Chowdhury, S. et al. (2011) Bioorg. Med. Chem. Lett. 21, 3676.
Alomone Labs XEN907 blocks NaV1.7 channels expressed in Xenopus oocytes.A. Time course of NaV1.7 current amplitude and inhibition by 10 µM XEN907 (#X-105). Currents were elicited by application of a 100 ms voltage step to 0 mV (H.P= -70 mV, to induce inactivation), every 10 seconds. B. Superimposed example traces of current responses before and during perfusion of 10 µM XEN907, as indicated.
Voltage-gated sodium (NaV) channels contribute to physiological and pathophysiological electrical signaling in nerve and muscle cells. NaV1.7 is highly expressed on the axons of somatic afferent neurons and is thought to play an important role in the signaling of inflammatory pain.
XEN907 is a synthetic blocker of NaV1.7 channels. It has an effective concentration of 1 nM – 10 μM and an IC50 of 5 nM for NaV1.7 in its inactive state. XEN907 is highly specific for NaV1.7 and at a concentration of 10 μM was not found to have significant activity against some 63 receptors and transporters examined1. XEN907 is not toxic and has favorable hepatocyte metabolic stability in humans and dogs, although inhibition of CYP3A4 was observed in a recombinant human enzyme assay. XEN907 has 97% plasma protein binding property in rat. XEN907 exhibits modest bioavailability of 13% and a T0.5 of 2.6±0.1 hours. XEN907 is extensively distributed when administered intravenously and has a clearing rate of 9.4±1.7 (L/h/kg)1.
