Ph-HTBA is a mid-nanomolar affinity (Ki=78nM), brain permeable ligand of CaMKIIα hub domain binding site.
Ph-HTBA has good cellular permeability and low microsomal clearance and shows brain permeability after systemic administration to mice.
Ph-HTBA is a promising candidate for CaMKIIα-associated pharmacological interventions and future clinical development.
Ph-HTBA reduces Ca2+-stimulated CaMKIIα Thr286 autophosphorylation in primary cortical neurons and substrate phosphorylation of recombinant CaMKIIα, potentially contributing to its neuroprotective effect.
