Paxilline
(Synonyms: 蕈青霉素) 目录号 : GC11082Paxilline是一种致震颤真菌生物碱,可有效抑制高电导Ca2+ 激活K+ (BK)通道,IC50约为10nM,Ki=1.9nM。
Cas No.:57186-25-1
Sample solution is provided at 25 µL, 10mM.
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Paxilline is a tremor-causing fungal alkaloid that can effectively inhibit high-conductance Ca2+-activated K+ (BK) channels, with IC50 of approximately 10nM and Ki=1.9nM[1]. Paxilline affects the dynamic balance of intracellular calcium ions and the transmission of electrical signals by blocking BK channels, and is used to explore the reaction and mechanism of BK channels in cellular processes[2]. Paxilline also inhibits muscle/endoplasmic reticulum Ca2+ ATPase, IC50 = 5-50µM[3].
In vitro, Paxilline (4µM) treated HT 22 cells for 18 h had significant cytoprotective effects against glutamate-induced toxicity, independent of BKCa channel activity and oxidative stress induced by glutamate treatment[4]. Paxilline (30µM) treatment of U251 MG, U87 MG, U343 and U251 N glioma cell lines can enhance the TRAIL sensitivity of cells and induce cell apoptosis [5].
In vivo, Paxilline (2.2 and 4.4 µg/kg) administered intraperitoneally to C57BL/6 mice could eliminate tonic-clonic seizures in mice and also reduce the duration and intensity of epileptic seizures[6]. Paxilline (3µg/kg) significantly alleviated thalidomide-induced synaptic and cognitive dysfunction in mice via intraperitoneal injection[7].
References:
[1] Zhou Y, et al. Paxilline inhibits BK channels by an almost exclusively closed-channel block mechanism[J]. Gen Physiol. 2014 Nov;144(5):415-40.
[2] Jackson-Weaver, O., Paredes, D.A., Gonzalez Bosc, L.V., et al. Intermittent hypoxia in rats increases myogenic tone through loss of hydrogen sulfide activation of large-conductance Ca2+-activated potassium channels.[J].Circulation Research 108(12), 2011:1439-1447 .
[3] Knaus H G, McManus O B, Lee S H, et al. Tremorgenic indole alkaloids potently inhibit smooth muscle high-conductance calcium-activated potassium channels. [J]Biochemistry, 1994, 33(19): 5819-5828.
[4] Szewczyk K A .Glutamate-induced cell death in HT22 mouse hippocampal cells is attenuated by paxilline, a BK channel inhibitor[J].Mitochondrion, 2012.
[5]Kang Y J , Kim I Y , Kim E H ,et al.Paxilline enhances TRAIL-mediated apoptosis of glioma cells via modulation of c-FLIP, survivin and DR5[J].Experimental & Molecular Medicine, 2011, 43(1):24.
[6]Sheehan JJ, et al. Anticonvulsant effects of the BK-channel antagonist paxilline. Epilepsia [J].2009. 50(4):711-20.
[7]Tae-Yong Choi, Seung-Hyun Lee, Soo-Jeong Kim, et al. BK channel blocker paxilline attenuates thalidomide-caused synaptic and cognitive dysfunctions in mice[J].Scientific Reports volume 8, 2018: 17653.
Paxilline是一种致震颤真菌生物碱,可有效抑制高电导Ca2+ 激活K+ (BK)通道,IC50约为10nM,Ki=1.9nM[1]。Paxilline通过阻断BK通道,影响细胞内钙离子的动态平衡及电信号的传递,被用于探究BK通道在细胞过程中的反应和作用机理[2]。Paxilline还抑制肌/内质网Ca2+ ATP酶,IC50 = 5-50µM[3]。
在体外,Paxilline(4µM)处理HT 22细胞18h,具有显著的细胞保护作用,免受谷氨酸诱导的毒性,与谷氨酸处理诱导的BKCa通道活性和氧化应激无关[4]。paxilline(30µM)处理U251 MG、U87 MG、U343和U251 N胶质瘤细胞系,可以增强细胞的TRAIL敏感性,诱导细胞凋亡[5]。
在体内,Paxilline(2.2 and 4.4µg/kg)通过腹腔注射给予C57BL/6小鼠,可以消除小鼠的强直阵挛性发作,还可以减少癫痫发作的持续时间和强度[6]。Paxilline(3µg/kg)通过腹腔注射,显著减轻了沙利度胺引起的小鼠突触和认知功能障碍[7]。
| Cell experiment [1]: | |
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Cell lines |
HT22 cells |
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Preparation Method |
HT22 cells were treatment with 3mM glutamate, BKCa channel inhibitors and 4µM Paxilline. After 18h of incubation, the cell lysates were prepared according to the kit protocol. |
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Reaction Conditions |
4µM; 18h |
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Applications |
In the presence of 4µM paxilline, the cytotoxic effect of glutamate was almost completely blocked. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6 mice |
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Preparation Method |
C57BL/6 mice were injected with either 2.2 and 4.4µg/kg Paxilline, or vehicle. Paxilline injections were carried out with a 5µm solution in 0.05% DMSO. Thirty min post injection, scoring of seizure onset, number, and cumulative duration. |
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Dosage form |
2.2 and 4.4µg/kg; i.p. |
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Applications |
Paxilline was sufficient to eliminate tonic-clonic seizures in picrotoxin-treated animals. Paxilline reduced seizure duration and intensity in pentylenetetrazole-injected animals. |
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References: [1] Szewczyk K A .Glutamate-induced cell death in HT22 mouse hippocampal cells is attenuated by paxilline, a BK channel inhibitor[J].Mitochondrion, 2012. | |
| Cas No. | 57186-25-1 | SDF | |
| 别名 | 蕈青霉素 | ||
| 化学名 | (2R,4bS,6aR,12bS,12cR,14aS)-4b-hydroxy-2-(2-hydroxypropan-2-yl)-12b,12c-dimethyl-5,6,6a,7,12,12b,12c,13,14,14a-decahydro-2H-chromeno[5',6':6,7]indeno[1,2-b]indol-3(4bH)-one | ||
| Canonical SMILES | O[C@]1(C2=C3)[C@@](CC[C@@H]2O[C@H](C(C)(C)O)C3=O)(C)[C@](C(NC4=CC=CC=C54)=C5C6)(C)[C@@H]6CC1 | ||
| 分子式 | C27H33NO4 | 分子量 | 435.56 |
| 溶解度 | 10mg/mL in ethanol, 30mg/mL in DMSO, or in DMF | 储存条件 | Desiccate 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。 |
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| 制备储备液 | |||
 |
1 mg | 5 mg | 10 mg |
| 1 mM | 2.2959 mL | 11.4795 mL | 22.9589 mL |
| 5 mM | 0.4592 mL | 2.2959 mL | 4.5918 mL |
| 10 mM | 0.2296 mL | 1.1479 mL | 2.2959 mL |
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| 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 |
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| % 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，
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2.
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Quality Control & SDS
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- Purity: >98.00%
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