trek-2

ML353 (VU0478006) is a selective activator of TREK-1 and TREK-2 and a selective ligand (Ki =18.2 nM) for the mGlu5 Silencing Allosteric Modulator (SAM). ML353 has potential as a solution to the intrinsic activity or pharmacological blockade of SAM in vivo.

TWIK-1 TREK-1-IN-2 (Compound 2g) serves as an inhibitor of both TWIK-1 and TREK-1, targeting the TREK-1 homodimer and TWIK-1 TREK-1 heterodimer with IC50 values of 10.13 μM and 15.5 μM, respectively; additionally, it exhibits antidepressant properties [1].

BL-1249 is a selective and potent non-steroidal potassium channel activator with anti-inflammatory activity that activates K2P2.1 (TREK-1) and K2P10.1 (TREK-2).

ML402 (ZINC3671497) is an activator of TREK-1 and TREK-2 with EC50s of 13.7 μM and 5.9 μM.

ONO-2920632 is an orally active and CNS-penetrant TREK channel activator with EC50 values of 0.3 µM for TREK-1 and 2.8 µM for TREK-2. It demonstrates selectivity for other K2P channels, showing over 91-fold selectivity against TASK1, TASK2, TASK3, TRAAK, TWIK2, and 31-fold selectivity against TRESK. ONO-2920632 exhibits analgesic effects and is used in the study of pain, migraine, and neurological disorders.

11-deoxy-PGF2a, a selective activator of TREK-2 channels, stimulates DRG c-fiber nociceptor K2P currents and limits calcium influx.

ML335 is a selective activator of TREK-1 and TREK-2.

Lig4-4 is a TREK-1 current inhibitor (IC50 = 2.06 μM) that has demonstrated potential for use as a protective agent against cerebral ischemia. It has been postulated that the neuroprotective effects of Lig4-4 against cerebral ischemia may be attributed to the modulation of Bcl-2 and cleaved-caspase-3 expression, leading to the inhibition of neuronal apoptosis.

Spadin TFA, a natural peptide originating from a propeptide in blood, acts as a powerful TREK-1 channel inhibitor with an IC 50 of 10 nM. It boosts dorsal raphe nucleus 5-HT neurotransmission in mice, activates hippocampal CREB, and promotes neurogenesis. This compound is useful for antidepressant research [1] [2].