trek-1

TWIK-1/TREK-1-IN-3 is a selective and potent inhibitor of the potassium channel TREK-1, effectively inhibiting TREK-1 homodimers and TWIK-1/TREK-1 heterodimers containing two-pore-domain potassium (K2p) channels. TWIK-1/TREK-1-IN-3 exhibits antidepressant activity and can be utilized in the study of depression.

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.

Ropivacaine hydrochloride (Ropivacaine monohydrochloride) is the hydrochloride salt of ropivacaine, a local anesthetic of the amide type with analgesic activity.

Ropivacaine (LEA-103 HCl) is a local anaesthetic drug belonging to the amino amide group.

2,2,2-Trichloroethanol, the active form of the sedative hypnotic drug chloral hydrate, is an agonist for the nonclassical K2P channels TREK-1 (KCNK2) and TRAAK (KCNK4). It activates a nonclassical potassium channel in cerebrovascular smooth muscle and dilates the middle cerebral artery [1]. [1]. Nikhil K Parelkar, et al. 2,2,2-trichloroethanol Activates a Nonclassical Potassium Channel in Cerebrovascular Smooth Muscle and Dilates the Middle Cerebral Artery. J Pharmacol Exp Ther. 2010 Mar;332(3):803-10.

Ropivacaine hydrochloride monohydrate (LEA-103 HCl) is an anaesthetic agent and blocks impulse conduction in nerve fibres through inhibiting sodium ion influx reversibly.

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

TKIM is a TWIK-related potassium channel 1 (TREK-1) inhibitor, binding to the pocket of the intermediate (IM) state of TREK-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).

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

Compound 2a, identified as TWIK-1/TREK-1-IN-1, acts as an inhibitor of the TREK-1, a two-pore domain potassium channel (K2p) that forms TREK-1 homodimers and TWIK-1/TREK-1 heterodimers, both significant for its role as an antidepressant target. Furthermore, TWIK-1/TREK-1-IN-3, a related compound, selectively inhibits these channels with IC50 values of 9.36 μM for TREK-1 homodimers and 14.6 μM for TWIK-1/TREK-1 heterodimers, demonstrating antidepressant-like effects [1].

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].

A1899 is a effective and selective TASK-1 and TASK-3 antagonist.

(±)-C3001a is the racemic mixture of C3001a (CAS: 2415154-29-7). C3001a is a selective activator of the TREK channel within the two-pore-domain potassium channel (K2P) family. C3001a specifically binds to a cryptic site formed by P1 and TM4 in TREK-1, thereby promoting the selective regulation of TREK-1 activity. C3001a targets TREK channels in the peripheral nervous system, reducing the excitability of pain-sensing neurons.

A2793 is a dual inhibitor of TWIK-associated acid-sensitive K+ channel 1 (TASK-1)/TRESK, with an IC50 for mTRESK of 6.8 μM. It is more selective for TRESK, and relatively weaker for TREK-1 and TALK-1.

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.

TREK inhibitor-3 (Cpd8l) is a selective inhibitor of TREK-1 that can cross the blood-brain barrier, with an IC50 of 0.81 μM. It offers neuroprotective effects by significantly reducing cortical neuron death induced by oxygen-glucose deprivation/reoxygenation (OGD/R) and alleviating brain injury in middle cerebral artery occlusion/reperfusion (MCAO/R) model mice. TREK inhibitor-3 is utilized in ischemic stroke research.

Spadin Acetate is a natural peptide derived from a propeptide released in blood. Spadin Acetate is able to block the TREK-1 channel activity. Spadin Acetate binds specifically to TREK-1 with an affinity of 10 nM.

Ropivacaine mesylate, a long-acting amide local anaesthetic, is used for spinal block and effectively mitigates neuropathic pain. It achieves analgesia by reversibly inhibiting sodium ion influx in nerve fibers, thus blocking impulse conduction. Additionally, Ropivacaine acts as an inhibitor of the K2P (two-pore domain potassium channel) TREK-1, exhibiting an IC50 of 402.7 μM in COS-7 cell membranes.

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].

PE 22-28, a TREK-1 inhibitor exhibiting an IC50 value of 0.12 nM, is a 7 amino-acid peptide. It serves as a foundational sequence for the creation of analogs through chemical modifications and amino-acid substitution. This compound is utilized in depression research [1].

A2764 dihydrochloride is a highly selective inhibitor of TWIK-related spinal cord K+ channel (TRESK).

BML264 ((E)-N-(p-amylcinnamoyl) anthranilic acid) is a potent agonist of TREK-1 (a two-pore domain potassium channel). TREK-1 channels play a central role in regulating neuronal excitability, pain signaling, and cardiovascular function. BML264 is frequently utilized to study pathological conditions associated with TASK-1 dysfunction by modulating potassium currents to alleviate related neurological or metabolic disorders.