task-1

TASK-1-IN-1 is a potent and selective inhibitor of TASK-1 (Potassium Channel) with an IC50 of 148 nM, and exhibits a reduced inhibitory effect on the TASK-3 channel with an IC50 of 1750 nM. TASK-1-IN-1 also demonstrates anticancer effects.

L-Allylglycine is an amino acid derivative that reduces glutamate decarboxylase (GAD) activity by 60% when administered at a dose of 39.8 μmol g per hour ex vivo in mouse brain preparations. L-Allylglycine (1.2 mmol kg, i.p.) induces convulsions and decreases GABA concentration throughout the cerebellum, pons, medulla, striatum, cortex, and hippocampus in mice. Chronic administration (3.2 μg 0.5 μl per hour for 13 days) of L-allylglycine in rats increases locomotor activity in an open field test and impairs attention in the 5-choice serial reaction time task (5CSRTT). In vitro, L-allylglycine inhibits GAD only when used at high concentrations (1-80 mM). The more potent in vivo activity can be attributed to metabolic conversion of L-allylglycine to 2-keto-4-pentanoic acid, a more potent convulsant and GAD inhibitor.

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.

Doxapram hydrochloride hydrate (Doxapram HCl) effectively inhibits the function of TASK-1, TASK-3, and TASK-1 TASK-3 heterodimeric channels, displaying EC50 values of 410 nM, 37 μM, and 9 μM, respectively.

DCPIB, a known specific and potent inhibitor of volume-regulated anion channels (VRAC),DCPIB displayed superior selectivity toward TRESK with an IC50 of 0.14 μM, demonstrating at least 100-fold higher affinity over TREK1 TRAAK channels.

Doxapram (Dopram) is a respiratory stimulant that inhibits TASK-1, TASK-3, and TASK-1 TASK-3 heterodimer channels and is used to study ventilatory failure caused by apnea of ​​prematurity and exacerbation of chronic obstructive pulmonary disease.

DL-AP7, a competitive NMDA antagonist and anticonvulsant, blocks NMDA-induced convulsions and impairs learning performance in mice during a passive avoidance task [1].

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

Pyrithiamine hydrobromide, an inhibitor of thiamine metabolism that acts as a substrate for thiamine pyrophosphate kinase, causes neurologic symptoms similar to wernickke - korsakoff syndrome in animals.

A-971432 is a sphingosine-1-phosphate receptor 5 (S1P5) agonist that is selective for S1P5 over S1P1 and S1P3 (IC50s = 0.006, 0.362, and >10 µM, respectively). It inhibits forskolin-induced cAMP production in CHO cells expressing S1P5 (EC50 = 4.1 nM). A-971432 (1 µM) increases electrical resistance of hCMEC D3 cells in an in vitro blood-brain barrier model, indicating enhanced barrier integrity, and attenuates blood-brain barrier leakage in an R6 2 transgenic mouse model of Huntington's disease when administered at a dose of 0.1 mg kg.[1] [2] A-971432 (0.1 mg kg per day, i.p.) decreases the number of errors made in a horizontal ladder task and increases latency to fall in the rotarod test in R6 2 mice. It also increases spontaneous alternation in the t-maze in aged mice when administered at a dose of 0.1 mg kg.[1] References [1].Hobson, A.D., Harris, C.M., van der Kam, E.L., et al. Discovery of A-971432, an orally bioavailable selective sphingosine-1-phosphate receptor 5 (S1P5) agonist for the potential treatment of neurodegenerative disorders. J. Med. Chem. 58(23), 9154-9170 (2015).[2]. Di Pardo, A., Castaldo, S., Amico, E., et al. Stimulation of S1PR5 with A-971432, a selective agonist, preserves blood-brain barrier integrity and exerts therapeutic effect in an animal model of Huntington's disease. Hum. Mol. Genet. 27(14), 2490-2501 (2018).

PF-04449613 is a phosphodiesterase 9A (PDE9A) inhibitor (IC50= 22 nM).1It is selective for PDE9A over PDE1C (IC50= >1,000 nM), as well as over a variety of other PDEs, inhibiting PDE2-8, -10, and -11 activity by less than 30% in a panel of enzymes, ion channels, and transporters at 1 μM but does inhibit the human dopamine transporter (DAT; Ki= 293 nM). PF-04449613 (0.1-100 mg kg, s.c.) increases cerebrospinal fluid (CSF) levels of cyclic GMP (cGMP) in rats. Subcutaneous administration of PF-04449613 (10 mg kg) increases the rate of dendritic spine formation and elimination in mouse primary motor cortex pyramidal neuronsin vivo.2It increases the average running speed of mice in an accelerating rotarod task, indicating improved motor learning, at the same dose. 1.Claffey, M.M., Helal, C.J., Verhoest, P.R., et al.Application of structure-based drug design and parallel chemistry to identify selective, brain penetrant, in vivo active phosphodiesterase 9A inhibitorsJ. Med. Chem.55(21)9055-9068(2012) 2.Lai, B., Li, M., Hu, A., et al.The phosphodiesterase 9 inhibitor PF-04449613 promotes dendritic spine formation and performance improvement after motor learningDev. Neurobiol.78(9)859-872(2018)

ML365 is a novel selective small molecule inhibitor of TASK1(KCNK3).

AVE1231 is a TASK-1 channel blocker that inhibits TASK-1 and can be used in the study of atrial fibrillation.

BAY-747 (BAY 1165747) is an orally administered, brain-penetrant compound that stimulates soluble guanylate cyclase (sGC). It effectively counteracts memory impairments induced by L-NAME, improves cognitive performance in rats during the object location task (OLT), reduces blood pressure in conscious normotensive and spontaneously hypertensive rats (SHR), and enhances skeletal muscle function in the mdx mTRG2 mouse model of Duchenne muscular dystrophy (DMD) [1] [2] [3].

NPBA, a potassium K2P channel TASK-3 (KCNK9) agonist, concurrently functions as a blocker of the tandem pore domain weak inward rectifying K+ channel (TWIK2). This compound effectively inhibits NLRP3 inflammasome activation in macrophages [1].