Kv2.1-syntaxin inhibitor 15

Kv2.1-syntaxin inhibitor 15 (Kv2.1-syntaxin-IN-15, Cpd5) is a small molecule Kv2.1-syntaxin-binding inhibitor (IC50=5.5 uM) with neuroprotective properties.Kv2.1-syntaxin inhibitor 15 competitively binds syntaxin against C1aB-containing Kv2.1 peptides with IC50 of 5.5 uM.Kv2.1-syntaxin inhibitor 15 (10 uM) significantly diminished threo-β-benzyloxyaspartate (TBOA, 75 uM)-induced toxicity neuronal cultures, ameliorated significant cellular damage, by preventing the expression of enhanced Kv2.1-mediated K+ currents.Kv2.1-syntaxin inhibitor 15 is a first-in-class inhibitor of Kv2.1 binding to Syntaxin, likely due to inhibition of the C1a region of Kv2.1 binding to syntaxin.Cpd5 (10 μM) does not affect evoked AMPAR EPSCs in layer 2/3 corticocallosal neurons in the mouse auditory cortex.

1. Yeh CY, et al. Proc Natl Acad Sci U S A. 2019 Jul 30;116(31):15696-15705.