3D Pharmacophore-Based Discovery of Novel K_V10.1 Inhibitors with Antiproliferative Activity.

ABSTRACT: (1) Background: The voltage-gated potassium channel K_V10.1 (Eag1) is considered a near- universal tumour marker and represents a promising new target for the discovery of novel anticancer drugs. (2) Methods: We utilized the ligand-based drug discovery methodology using 3D pharmacophore modelling and medicinal chemistry approaches to prepare a novel structural class of K_V10.1 inhibitors. Whole-cell patch clamp experiments were used to investigate potency, selectivity, kinetics and mode of inhibition. Anticancer activity was determined using 2D and 3D cell-based models. (3) Results: The virtual screening hit compound ZVS-08 discovered by 3D pharmacophore modelling exhibited an IC₅₀ value of 3.70 µM against K_V10.1 and inhibited the channel in a volt

SUBMITTER: Toplak Z 

PROVIDER: S-EPMC8002023 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature