XEN907 is a novel spirooxindole NaV1.7 blocker, inhibits hNaV1.7 with IC50 of 3 nM.IC50 value: 3 nMTarget: NaV1.7in vitro: XEN907 shows a further 10-fold increase in potency, represents a promising structure for further optimization efforts. XEN907 shows no significant activity at 10 μM against a broad panel of 63 receptors and transporters. Determination of the ADME properties of XEN907 reveals that XEN907 is not cytotoxic and has favourable hepatocyte metabolic stability for both human and dog, although inhibition of CYP3A4 is observed in a recombinant human enzyme assay.[1]in vivo: Pharmacokinetic analysis in rats of XEN907 demonstrates that, consistent with the compound's ADME parameters, the compound is modestly bioavailable. Following an initial rapid absorption phase (oral Tmax = 20 min), XEN907 is extensively distributed (Vss 600-fold higher than the plasma volume in rats) and rapidly cleared. [1]
[1]. Chowdhury S, et al. Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3676-81.