Pain ReliefThe treatment of pain in both its acute and chronic forms remains a significant clinical challenge. Many intricate and overlapping physiological systems contribute to pain states, and there are numerous pathways identified as possible targets for intervention. Chromocell focused its drug discovery program in pain on Nav1.7, a voltage-gated sodium ion channel validated as a relevant target for pain therapy. Chromovert® technology has allowed the creation of cell lines expressing not only the pore forming alpha subunit but also auxiliary beta subunits critical for physiological activity. Working with cell lines that express all subunits of the drug target is expected to enhance the discovery success rate. To date, research in the field has been limited to working with suboptimal cell lines that do not express all subunits whereas we are now able to screen the target in its complete form. Several lead chemical series are currently in the optimization process in preparation for candidate selection, preclinical development and ultimately, human clinical trials.
Respiratory DisordersChromocell has a discovery program to identify compounds for the treatment of pulmonary pathologies. The target is the epithelial sodium channel, ENaC, an ion channel comprising three distinct subunits which has never been reduced to a cell-based assay due to the toxicity of its over-expression. Modulation of this channel impacts several pulmonary conditions, including pulmonary edema, COPD and cystic fibrosis. Applying Chromovert technology and a multi-pronged approach exploring various cell backgrounds and media formulations, we have been able to isolate functional and viable clonal cell lines for this target. A high-throughput screening campaign has been carried out and hits were identified representing agonists, antagonists and positive modulators. The most promising compounds are being progressed through lead optimization to candidate selection.
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