Overview
- Murray, J.K. et al. (2015) J. Med. Chem. 58, 2299.
- Murray, J.K. et al. (2015) Bioorg. Med. Chem. Lett. 25, 4866.
Alomone Labs GpTx-1 inhibits NaV1.7 channels expressed in Xenopus oocytes.A. Time course of GpTx-1 (#STG-400) inhibition of NaV1.7 channels current. Membrane potential was held at -100 mV, current was elicited by a 100 ms voltage step to 0 mV every 10 sec, and inhibited by 200 nM GpTx-1 (bar), applied for 10 min. B. Superimposed traces of NaV1.7 channel currents upon application of control and of 200 nM GpTx-1 (as indicated), taken from the recording shown in A.
GpTx-1 is a 34-residue peptide with inhibitory cystine knot motif and contains 3 important residues near the C-terminus that are critical for potently blocking NaV1.7 channel, with IC50 value of 10 nM. The peptide toxin was originally isolated from the Grammostola porteri spider venom1,2. In addition, GpTx-1 demonstrates selectivity against other NaV subtypes including NaV1.4 and NaV1.5 channels.
There are nine mammalian subtypes of voltage-gated sodium (NaV) channels: NaV1.1–NaV1.9. These channels responsible for propagating action potentials in excitable cells and are considered to be important therapeutic targets for a wide variety of pathophysiological conditions such as cardiac arrhythmia, and epilepsy. NaV1.7 channel plays an important role in human pain signalling pathway and it is an important therapeutic target for treatment of chronic pain3,4.
