XEN907

• CAT Number: I005441
• CAS Number: 912656-34-9
• Molecular Formula: C21H21NO4
• Molecular Weight: 351.402
• Purity: ≥95%
• Target: NaV1.7
• Solubility: 10 mM in DMSO
• Storage: Store at -20°C
• IC50: 3 nM
• IUPAC Name: 1/'-pentylspiro[6H-furo[2,3-f][1,3]benzodioxole-7,3/'-indole]-2/'-one
• InChI: InChI=1S/C21H21NO4/c1-2-3-6-9-22-16-8-5-4-7-14(16)21(20(22)23)12-24-17-11-19-18(10-15(17)21)25-13-26-19/h4-5,7-8,10-11H,2-3,6,9,12-13H2,1H3
• InChIKey: PHMRUZIIERITEP-UHFFFAOYSA-N
• SMILES: CCCCCN1C2=CC=CC=C2C3(C1=O)COC4=CC5=C(C=C34)OCO5

XEN907 (CAT: I005441) is a potent spiro oxindole compound that acts as a selective inhibitor of the NaV1.7 sodium channel, with an IC50 value of 3 nM. This compound exhibits strong inhibitory activity against NaV1.7 and shows no significant interaction with other receptors and transporters. XEN907 has potential applications in the development of drugs targeting pain and other conditions associated with NaV1.7 dysfunction. It demonstrates favorable ADME properties, including hepatocyte metabolic stability and moderate bioavailability. XEN907 holds promise as a therapeutic candidate for the treatment of pain and further optimization efforts to enhance its potency and selectivity are underway.

Reference

1. Bioorg Med Chem Lett. 2011 Jun 15;21(12):3676-81. doi: 10.1016/j.bmcl.2011.04.088. Epub 2011 Apr 24.
Discovery of XEN907, a spirooxindole blocker of NaV1.7 for the treatment of pain.
Chowdhury S(1), Chafeev M, Liu S, Sun J, Raina V, Chui R, Young W, Kwan R, Fu J, Cadieux JA.
Author information:
(1)Department of Medicinal Chemistry, Xenon Pharmaceuticals Inc., Burnaby, British Columbia, Canada.
Starting from the oxindole 2a identified through a high-throughput screening campaign, a series of Na(V)1.7 blockers were developed. Following the elimination of undesirable structural features, preliminary optimization of the oxindole C-3 and N-1 substituents afforded the simplified analogue 9b, which demonstrated a 10-fold increase in target potency versus the original HTS hit. A scaffold rigidification strategy then led to the discovery of XEN907, a novel spirooxindole Na(V)1.7 blocker. This lead compound, which in turn showed a further 10-fold increase in potency, represents a promising structure for further optimization efforts.