Voltage-Gated Sodium Channel Na_V1.7 Inhibitors with Potent Anticancer Activities in Medullary Thyroid Cancer Cells.

ABSTRACT: Our results from quantitative RT-PCR, Western blotting, immunohistochemistry, and the tissue microarray of medullary thyroid cancer (MTC) cell lines and patient specimens confirm that VGSC subtype Na_V1.7 is uniquely expressed in aggressive MTC and not expressed in normal thyroid cells and tissues. We establish the druggability of Na_V1.7 in MTC by identifying a novel inhibitor (SV188) and investigate its mode of binding and ability to inhibit I_Na current in Na_V1.7. The whole-cell patch-clamp studies of the SV188 in the Na_V1.7 channels expressed in HEK-293 cells show that SV188 inhibited the I_Na current in Na_V1.7 with an IC₅₀ value of 3.6 µM by a voltage- and use-depende

SUBMITTER: Pukkanasut P 

PROVIDER: S-EPMC10216335 | biostudies-literature | 2023 May

REPOSITORIES: biostudies-literature