PK-THPP

PK-THPP is a potent and brain-penetrant TWIK-related acid-sensitive K⁺ ion channel (K2P9.1 or TASK-3) blocker with IC₅₀s of 35 nM and 300 nM for TASK-3 and TASK-1, respectively. PK-THPP shows no or less activity against other K⁺ channels. PK-THPP is an effective breathing stimulant and can be used for the study of breathing disorders^[1][2]. In Vitro:PK-THPP (compound 23) is inactive against the K2P channels TREK-1 (IC₅₀ >10 000 nM). PK-THPP is weakly active against the voltage-gated Kv1.5 (IC₅₀ ~5 µM), insensitive to hERG at the highest test concentration (>15 µM), and does not inhibit KATP (<10% inhibition at 10 µM). PK-THPP shows no activity being observed against more than 100 different receptors, ion channels and enzymes (10 µM exposure)^[1]. In Vivo:PK-THPP (15-100 mg/kg; s.c. 3-5 days) has the ability to regulate sleep architecture in rodent electroencephalogram (EEG) telemetry models^[1].