task

TASK-1-IN-1 是一种有效的选择性的 TASK-1 (Potassium Channel) 抑制剂（IC50 ： 148 nM）。TASK-1-IN-1 对 TASK-3 通道 的IC50 为 1750 nM，抑制作用有所降低。TASK-1-IN-1 具有抗癌作用。

CHET3 是一种含 TASK-3 的 K2P 通道的高度选择性变构激活剂。CHET3 在啮齿动物的各种急性和慢性疼痛模型中显示出强大的体内镇痛作用。

L-Allylglycine 是 GABA 合成酶（谷氨酸脱羧酶）的有效抑制剂。

AVE1231 是一种 TASK-1 通道阻滞剂，抑制 TASK-1 ，可用于研究心房颤动。

A2793 是 TWIK 相关酸敏感 K+通道 1(TASK-1)/TRESK 的双重抑制剂，对 mTRESK 的 IC50为 6.8 μM。它对 TRESK 选择性更好, 对 TREK-1 和 TALK-1 相对弱一些。

Bupivacaine is a BK/SK, Kv1, Kv3, TASK-2 K Channel and voltage-gated Na channel blocker used as an anesthetic. It maybe neurotoxic at high does, inducing apoptosis in neuroblastoma cells. It acts by binding to the intracellular portion of voltage-gated sodium channels and blocking sodium influx into nerve cells.

BAY-747 (BAY 1165747) 为一种通过口服生效且具有脑渗透性的sGC刺激剂。它能可逆地逆转L-NAME所诱导的记忆障碍并在大鼠中增强认知功能。BAY-747还可在有意识状态下降低正常血压及自发性高血压大鼠(SHR)的血压。此外，BAY-747在mdx mTRG2小鼠模型中改善了与Duchenne肌营养不良症(DMD)相关的骨骼肌功能。

DL-AP7 是一种竞争性NMDA 拮抗剂和抗惊厥剂。DL-AP7 阻断 NMDA 诱导的惊厥,并导致小鼠在被动回避任务中的学习表现受损。

ML365 是有效的，选择性的双孔结构域钾通道TASK1/KCNK3抑制剂，IC50为 4 nM。它可用于检查 TASK1 通道的特定作用。

Pyrithiamine is the pyridine analog of thiamine that prevents growth of organisms that require intact thiamine. [1] It inhibits the growth of bacterial and fungal species at a pyrithiamine:thiamine ratio of 10:1 in growth media and induces symptoms of thiamine deficiency in mice at a dietary ratio of 3:1. These effects are reversible with addition of sufficient thiamine in all species. Pyrithiamine inhibits the formation of cocarboxylase from thiamine in chicken blood in a dose-dependent manner. [2] It has been used to induce thiamine deficiency in various disease models, including rat models of alcoholism and diencephalic amnesia, to study the effects of thiamine deficiency on disease pathology.[3] [4] Reference：[1]. Woolley, D.W., and White, A.G.C. Selective reversible inhibition of microbial growth with pyrithiamine. J. Exp. Med. 78(6), 489-497 (1943).[2]. Woolley, D.W. An enzymatic study of the mode of action of pyrithiamine (neopyrithiamine). J. Biol. Chem. 191(1), 43-54 (1951).[3]. Vetreno, R.P., Anzalone, S.J., and Savage, L.M. Impaired, spared, and enhanced ACh efflux across the hippocampus and striatum in diencephalic amnesia is dependent on task demands. Neurobiol. Learn Mem. 90(1), 237-244 (2008).[4]. Zahr, N.M., Sullivan, E.V., Rohlfing, T., et al. Concomitants of alcoholism: Differential effects of thiamine deficiency, liver damage, and food deprivation on the rat brain in vivo. Psychopharmacology (Berl) 233(14), 2675-2686 (2016).

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)

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

NPBA为K2P通道TASK-3 (KCNK9)的激动剂，并对串联孔域弱内向整流K+通道(TWIK2)具有阻断作用。此外，NPBA能够抑制巨噬细胞中NLRP3炎性体的激活。

Doxapram hydrochloride hydrate (Doxapram HCl) 是 TASK-1，TASK-3和 TASK-1 TASK-3异二聚体通道的抑制剂，EC50分别为410 nM，37 μM 和9 μM。

PK-THPP is a channel blocker of TASK-3.

Doxapram, a central respiratory stimulant with a brief duration of action, is a selective TASK-1, TASK-3, TASK-1 TASK-3 heterodimeric channel inhibitor with EC50 of 410 nM, 37 μM, 9 μM, respectively.