GX-674 is an aryl sulfonamide class of antagonist that inhibits Nav1.7 channel with an IC50 value of 0.1nM [1]. GX-674 binds to the chimeric VSD4-NavAb channel with high affinity and inhibits the inactivation of VSD4, thereby stabilizing the inactivated state of Nav1.7[2]. GX-674 has been widely used as a model compound to investigate the interaction between mutant R1608A and GX-674, as well as to analyze the binding sites that affect the selectivity of the drug in the biochemical experiments[3].
References:
[1] Payandeh J, Hackos D H. Selective ligands and drug discovery targeting the voltage-gated sodium channel Nav1. 7[J]. Voltage-gated Sodium Channels: Structure, Function and Channelopathies, 2018: 271-306.
[2] Ahuja S, Mukund S, Deng L, et al. Structural basis of Nav1. 7 inhibition by an isoform-selective small-molecule antagonist[J]. Science, 2015, 350(6267): aac5464.
[3] Pukkanasut P, Jaskula-Sztul R, Gomora J C, et al. Therapeutic targeting of voltage-gated sodium channel NaV1. 7 for cancer metastasis[J]. Frontiers in Pharmacology, 2024, 15: 1416705.
GX-674是一种芳基磺酰胺类拮抗剂，可抑制Nav1.7通道，IC50值为0.1nM[1]。GX-674以高亲和力结合至嵌合型VSD4-NavAb通道，并抑制VSD4的失活，从而稳定Nav1.7的失活状态[2]。GX-674已被广泛用作模型化合物，用于研究突变体R1608A与GX-674之间的相互作用，并在生化实验中分析影响药物选择性的结合位点[3]。