Stroke is the second leading cause of death and the leading cause of disability worldwide. Even where advanced technology and facilities are available, 60 percent of those who suffer a stroke die or suffer other outcomes like loss of mobility, impaired speech, or cognitive disabilities. The irreversible harm caused by interrupting blood flow to the brain unfolds hours to days after the initial blockage, so it is critical to identify early interventions that could reduce neuronal death. Several studies have suggested that upregulated Na+-K+-Cl- cotransporter (NKCC) activity in the brain plays a direct role in stroke-related cell death, which has led to interest in the NKCC blocker bumetanide. Although bumetanide has shown promise in animal models of stroke, its potent diuretic action and poor passage through the blood-brain barrier present significant limitations for its use in humans. Our novel class of NKCC1 inhibitors address bumetanide’s shortcomings to provide a safer and more effective early stroke intervention.
Luo, L., Wang, J., Ding, D., Hasan, M. N., Yang, S.-S., Lin, S.-H., Schreppel, P., Sun, B., Yin, Y., Erker, T., & Sun, D. (2020). Role of NKCC1 Activity in Glioma K+ Homeostasis and Cell Growth: New Insights With the Bumetanide-Derivative STS66. Frontiers in Physiology, 11. https://doi.org/10.3389/fphys.2020.00911
Huang, H., Bhuiyan, M. I. H., Jiang, T., Song, S., Shankar, S., Taheri, T., Li, E., Schreppel, P., Hintersteininger, M., Yang, S.-S., Lin, S.-H., Molyneaux, B. J., Zhang, Z., Erker, T., & Sun, D. (2019). A Novel Na + -K + -Cl − Cotransporter 1 Inhibitor STS66* Reduces Brain Damage in Mice After Ischemic Stroke. Stroke, 50(4), 1021–1025. https://doi.org/10.1161/strokeaha.118.024287