ASP2905是一种新型的、具有口服活性的钾通道KCNH3抑制剂。
Cas No.:792184-90-8
Sample solution is provided at 25 µL, 10mM.
_1-3.$$$39978408@51.jpg');)
_1-9.$$$38538795@65.jpg');)
_1-9.$$$39112701@51.jpg');)
_1-7.$$$37316672@70.jpg');)
_366-372.$$$36198801@70.jpg');)
.$$$38565142@65.jpg');)
_1867-1883.$$$33248023@67.jpg');)
_eads6055.$$$39977546@45.jpg');)
_eadm9805.$$$40080571@45.jpg');)
_eadj3020.$$$39666821@45.jpg');)
_1-20.$$$39757301@28.jpg');)
_1-24.$$$38898113@28.jpg');)
_273-287.$$$36806353@46.jpg');)
_1-16.$$$37156877@44.jpg');)
_1-19.$$$37460805@44.jpg');)
_1291-1307.$$$34518654@46.jpg');)
ASP2905 is a novel, orally active potassium channel KCNH3 inhibitor. ASP2905 can cross the blood-brain barrier to exert antipsychotic effects, while also improving neuropsychiatric symptoms by enhancing cognitive function. ASP2905 is applicable for research in attention-deficit/hyperactivity disorder and schizophrenia[1-2].
In vitro, ASP2905 (0.1–10μM) was applied to HEK293 cells for approximately 2 days. ASP2905 bound to aptazyme- and exon skipping-based riboswitches, significantly upregulating the expression of the reporter gene EGFP, with no significant effect on the viability of HEK293 cells[3]. ASP2905 (0.1–1μM) was administered to primary cultured rat hippocampal neurons for 4 minutes. ASP2905 significantly decreased both the frequency and mean amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs)[4].
In vivo, ASP2905 (0.0313–0.3 mg/kg; orally) was administered to normal ddY mice and juvenile stroke-prone spontaneously hypertensive rats (SHRSP). ASP2905 significantly shortened the finding latency in mice, prolonged the cumulative latency in rats, and concurrently increased the extracellular levels of dopamine and acetylcholine in the medial prefrontal cortex of rats, as well as the alpha band power in electroencephalograms[5]. ASP2905 (0.03–0.3mg/kg; oral administration) was used to treat a mouse model of schizophrenia. ASP2905 significantly reversed the prolonged immobility time in the forced swim test, shortened the finding latency in neonatal mice, and markedly ameliorated the hyperlocomotor activity in mice[6].
References:
[1] Nomura Y, Kim N, Zhu B, et al. Optimization of Exon-Skipping Riboswitches and Their Applications to Control Mammalian Cell Fate. ACS Synth Biol. 2024 Oct 18;13(10):3246-3255.
[2] Ishii Y, Fukunaga K, Cooney A, et al. Switchable and orthogonal gene expression control inside artificial cells by synthetic riboswitches. Chem Commun (Camb). 2024 Jun 4;60(46):5972-5975.
[3] Fukunaga K, Dhamodharan V, Miyahira N, et al. Small-Molecule Aptamer for Regulating RNA Functions in Mammalian Cells and Animals. J Am Chem Soc. 2023 Apr 12;145(14):7820-7828.
[4] Takahashi S, Inamura K, Yarimizu J, et al. Neurochemical and neuropharmacological characterization of ASP2905, a novel potent selective inhibitor of the potassium channel KCNH3. Eur J Pharmacol. 2017 Sep 5;810:26-35.
[5] Takahashi S, Ohmiya M, Honda S, et al. The KCNH3 inhibitor ASP2905 shows potential in the treatment of attention deficit/hyperactivity disorder. PLoS One. 2018 Nov 21;13(11):e0207750.
[6] Takahashi S, Okamura A, Yamazaki M, et al. ASP2905, a specific inhibitor of the potassium channel Kv12.2 encoded by the Kcnh3 gene, is psychoactive in mice. Behav Brain Res. 2020 Jan 27;378:112315.
ASP2905是一种新型的、具有口服活性的钾通道KCNH3抑制剂。ASP2905可穿越血脑屏障来发挥抗精神病作用，同时通过增强认知功能以改善神经精神症状。ASP2905可用于注意力缺陷/多动障碍和精神分裂症的相关研究[1-2]。
在体外，ASP2905（0.1–10μM）处理HEK293细胞约2天，ASP2905能够结合基于aptazyme和外显子跳跃的核糖开关，显著上调报告基因EGFP的表达，对HEK293细胞的活性无显著影响[3]。ASP2905（0.1–1μM）处理原代培养的大鼠海马神经元4分钟。ASP2905能够显著降低自发抑制性突触后电流（sIPSCs）的频率和平均振幅[4]。
在体内，ASP2905（0.0313–0.3mg/kg；口服）处理正常ddY小鼠及幼年易卒中自发性高血压大鼠（SHRSP）。ASP2905能够显著缩短小鼠的寻找潜伏期，并延长大鼠的累积潜伏期，同时增加大鼠内侧前额叶皮层中多巴胺和乙酰胆碱的细胞外水平以及脑电图的α波段功率[5]。ASP2905（0.03–0.3mg/kg；口服给药）处理精神分离小鼠模型。ASP2905能够显著逆转小鼠在强迫游泳测试中不动时间的延长，并显著缩短新生期小鼠的寻找潜伏期，同时显著改善小鼠的自发活动亢进[6]。
| Cell experiment [1]: | |
Cell lines | HEK293 cells (human embryonic kidney 293 cell line) |
Preparation Method | HEK293 cells were co-transfected with an EGFP-riboswitch plasmid containing the aptamer AC17-4 integrated into a circularly-permuted pistol (CPP) ribozyme scaffold (a8-AC17-4-CPP) in the 3' UTR, and an mCherry-expressing plasmid as a transfection control. Cells were cultured in the absence or presence of ASP2905 (0.1–10μM). |
Reaction Conditions | 0.1–10μM; 2 day. |
Applications | ASP2905 significantly activated gene expression from the riboswitch construct, leading to an approximately 10-fold upregulation of EGFP fluorescence compared to the no-ligand control. |
| Animal experiment [2]: | |
Animal models | ddY mice, juvenile stroke-prone spontaneously hypertensive rats (SHRSP) |
Preparation Method | For the water finding task, normal ddY mice were orally administered ASP2905 (0.0313 and 0.0625mg/kg) 30 minutes before a training trial. Mice were then water-deprived until the test trial on the following day. For the five-trial passive avoidance task, juvenile SHRSP rats (4 weeks old) were administered ASP2905 (0.1 and 0.3mg/kg; orally) 30 minutes before the acquisition trials. |
Dosage form | 0.0313-0.3mg/kg; p.o.; Single administration 30 minutes before behavioral testing. |
Applications | ASP2905 significantly shortened the finding latency (an index of latent learning/attention) of mice in the water finding task. ASP2905 significantly prolonged the cumulative latency of juvenile SHRSP rats (a model of ADHD) in the five-trial passive avoidance task, indicating an improvement in attention deficits and impulsivity. |
References: | |
| Cas No. | 792184-90-8 | SDF | |
| Canonical SMILES | FC1=CC=C(NC2=NC(NC3=CC=CC=C3)=NC(NCC4=NC=CC=N4)=N2)C=C1 | ||
| 分子式 | C20H17FN8 | 分子量 | 388.4 |
| 溶解度 | DMSO : 100 mg/mL (257.47 mM; Need ultrasonic) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
||
| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.5747 mL | 12.8733 mL | 25.7467 mL |
| 5 mM | 514.9 μL | 2.5747 mL | 5.1493 mL |
| 10 mM | 257.5 μL | 1.2873 mL | 2.5747 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Quality Control & SDS
- View current batch:
- Purity: >98.00% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet