Recent efforts have rapidly expanded the chemical diversity of small molecule KCNT1 inhibitors and activators, providing a foundation for the rational design of next-generation targeted therapies.
Recent structure-activity relationship studies and drug repurposing efforts have expanded the chemical diversity of KCNT1 channel modulators, enabling rational design of future therapies.
probes identified through drug repurposing. This review provides an overview of the peer-reviewed literature describing chemotypes with structural features that enhance potency and selectivity compared to earlier KCNT1 modulators. Also discussed are structure-activity relationship (SAR) studies that have enabled the rational optimization of molecules to enhance overall drug-like properties. Together, these insights provide a foundation for the rational design of next generation KCNT1-targeted therapies. Progress in this field has been tremendous, and the chemical diversity of small molecule KCNT1 inhibitors has grown rapidly. While KCNT1 activators are rarer, progress has been made in this area as well.
Peprah et al. (Wed,) conducted a review in KCNT1 channel modulation. Small molecule modulators of KCNT1 channels was evaluated. Recent efforts have rapidly expanded the chemical diversity of small molecule KCNT1 inhibitors and activators, providing a foundation for the rational design of next-generation targeted therapies.