Zandatrigine

Zandatrigine (NBI-921352; XEN901) is a selective, orally active, voltage-gated sodium channel NaV1.6/SCN8A inhibitor that can penetrate the blood-brain barrier. Zandatrigine inhibits sodium influx by non-covalently binding to the VSD4 structure of NaV1.6, blocking the persistent and resuscitative currents under pathological conditions. Zandatrigine can reduce neuronal hyperexcitability and reduce epileptic seizures. Zandatrigine is 134-756-fold selective for other isoforms such as NaV1.1 and NaV1.2, and has minimal effect on NaV1.1 expressed by inhibitory interneurons. Zandatrigine can be used to study NaV1.6-mediated neuroexcitability diseases such as SCN8A-related developmental epileptic encephalopathy (SCN8A-DEE) and adult focal epilepsy[1][2].

Product Specifications

CAS Number

[2154406-04-7]

Product Name Alternative

NBI-921352; XEN901

UNSPSC

12352005

Target

Sodium Channel

Type

Reference compound

Related Pathways

Membrane Transporter/Ion Channel

Applications

Neuroscience-Neuromodulation

Field of Research

Neurological Disease

Assay Protocol

https://www.medchemexpress.com/zandatrigine.html

Purity

99.28

Solubility

DMSO : 125 mg/mL (ultrasonic)

Smiles

CN([C@@H]1CN(CC1)CC2=CC=CC=C2)C3=C(C=C(C(F)=C3)S(NC4=CSC=N4)(=O)=O)C

Molecular Formula

C22H25FN4O2S2

Molecular Weight

460.59

References & Citations

[1]Bay S, et al. Synthesis and Characterization of Click Chemical Probes for Single-Cell Resolution Detection of Epichaperomes in Neurodegenerative Disorders. Biomedicines. 2024 Jun 4;12 (6) :1252.|[2]Johnson JP, et al. Epileptogenic Channelopathies Guide Design of NBI-921352, a Highly Isoform-Selective Inhibitor of NaV1.6. In: Noebels JL, Avoli M, Rogawski MA, Vezzani A, Delgado-Escueta AV, editors. Jasper's Basic Mechanisms of the Epilepsies. 5th ed. New York: Oxford University Press; 2024. Chapter 72.