ZT-1a

ZT-1a is a potent and selective, non-ATP competitive inhibitor of SPAK-NKCC1 signaling. It inhibits SPAK activity with an IC50 of 44.3µM. Blocking the SPAK–NKCC1 cascade prevents excessive ion influx (Na⁺, K⁺, Cl⁻), which is triggered by oxidative stress. Inhibition of this pathway helps maintain cellular ion homeostasis, reduces oxidative stress-induced apoptosis, and protects the integrity of the blood–CSF barrier. Blocking SPAK–NKCC1 also mitigates neuroinflammation by reducing immune cell infiltration, thus offering neuroprotection in both in vitro and in vivo models.