1.D.322.  The Synthetic Chloride Transporters (SClTr) Family

The development of synthetic compounds capable of transporting chloride anions across biological membranes has been productive. Progress was driven by the desire to develop treatments for chloride transport related diseases (e.g., cystic fibrosis), cancer or bacterial infections. Chowdhury et al. 2025 used high-throughput screening and machine learning to identify novel scaffolds, and to find the molecular features needed to achieve potent chloride transport that can be generalized across diverse chemotypes. 1894 compounds were tested, 59 of which had confirmed transmembrane chloride transport ability. A machine learning (ML) binary classification model indicated that MolLog P is the most important feature to predict transport ability, but it is not sufficient by itself. The best ML model was able to identify potential chloride transporters from the DrugBank database, and the predictions were experimentally validated (Chowdhury et al. 2025). These insights provide other researchers with guidelines to develop ever more potent chloride transporters.

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