task-1-in-1

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。

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。

Doxapram (hydrochloride) 是一种呼吸兴奋剂，可抑制 TASK 背景钾通道（K2P）的功能。其对 TASK-1 和 TASK-3 的抑制作用的 EC50 值分别为 410 nM 和 37 nM，而对 TASK-1/TASK-3 异二聚体通道的抑制作用的 EC50 值为 9 μM。Doxapram (hydrochloride) 可用于研究早产儿呼吸暂停症。

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。

Pyrithiamine hydrobromide（啶硫胺氢溴酸盐）是一种硫胺素代谢抑制剂，作为硫胺素焦磷酸激酶的底物发挥作用，在动物中引起类似wernickke - korsakoff综合征的神经系统症状。

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)

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。

NPBA 是一种双功能小分子，同时是钾离子双孔域通道 TASK-3 (KCNK9) 的激动剂和串联孔域弱内向整流钾通道 TWIK2 的阻断剂。NPBA 能够显著抑制巨噬细胞中 NLRP3 炎症小体的活化。

BML264 ((E)-N-(p-amylcinnamoyl) anthranilic acid) 是一种有效的 TREK-1 (双孔结构域钾通道) 激动剂。TREK-1 通道在调节神经元兴奋性、痛觉传导及心血管功能中起着核心作用。BML264 常被用于研究与 TASK-1 功能障碍相关的病理状态，通过调节钾离子电流来改善相关的神经或代谢紊乱。