Targeting the Oncogenic hEag1 Ion Channel: Developing Venom Peptide-Based Pharmacological Tools

ongoing

The human ether à go-go 1 (hEag1) ion channel, also known as Kv10.1, is a voltage-gated potassium channel that is highly expressed in the brain but remains largely absent in other tissues under healthy conditions. However, during cancer development, hEag1 is significantly upregulated in various tumours, making it a potential biomarker and therapeutic target. Its role in cancer, particularly in breast cancer, is still not well understood, which makes exploring hEag1 a critical focus of my research. In this project, I aim to discover and develop the first series of selective hEag1 ligands that can be used as pharmacological probes and therapeutic leads to investigate the channel's function in breast cancer. Building on preliminary data, I will utilize the rich pharmacological diversity found in animal venoms to identify novel peptide ligands that target hEag1. Through structure-activity relationship (SAR) studies and advanced medicinal chemistry, I plan to enhance the potency and selectivity of both newly discovered and existing ligands. These optimized compounds will enable me to explore the functional role of hEag1 in breast cancer progression and assess its therapeutic potential. By integrating peptide chemistry, pharmacology, and preclinical methodologies, this research will pave the way for the creation of highly specific hEag1-targeting probes and drugs. The ultimate goal is to deepen our understanding of hEag1's role in breast cancer and unlock new avenues for targeted cancer therapy, especially for aggressive forms like triple-negative breast cancer.