PK 11195
(Synonyms: 1-(2-氯苯基)-N-甲基-N-(1-甲基丙基)-3-异喹啉甲酰胺,RP 52028) 目录号 : GC16569
PK 11195是一种异喹啉甲酰胺衍生物，作为非苯二氮䓬类转运蛋白（TSPO）选择性配体。
Cas No.:85532-75-8
Sample solution is provided at 25 µL, 10mM.
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PK 11195 is an isoquinoline carboxamide derivative and a non-benzodiazepine translocator protein (TSPO) selective ligand[1]. PK 11195 selectively labeled microglia in the central nervous system (CNS), and PK 11195 binding was significantly increased in activated microglia[2]. PK11195 has been widely used as a neuroimaging agent in positron emission tomography (PET) studies and as a neuromodulator to control neurological function in animal models[3].
In vitro, PK 11195 treatment for 72h inhibited cell viability of MCF-7 and T47D cells, with IC50 values of 5.4 and 6.0nM[4]. PK 11195 treatment for 72 hours significantly inhibited the viability of IOMM-LEE cells with an IC50 value of 1.505 ± 0.08nM, and reversed the increase in allopregnanolone level promoted by AC-5216[5]. Treatment with 50μM PK 11195 for 24h inhibited SMS-KCN proliferation, induced apoptosis, and caused G1/S cell cycle arrest, accompanied by decreased mRNA expression of chemotherapy resistance efflux pumps ABCA3, ABCB1, and ABCC1[6].
In vivo, PK 11195 (3mg/kg/day) administered intraperitoneally to C57/BL6 mice for 14 consecutive days prevented cognitive dysfunction induced by systemic lipopolysaccharide (500μg/kg/day; i.p.) injection, reduced neuroinflammation, and increased neurosteroid synthesis[7]. Intraperitoneal injection of PK 11195 (3 mg/kg/week for 5 weeks) in 16-month-old female 3xTg-AD mice improved cognitive and behavioral performance and reduced both soluble and deposited β-amyloid[8].
References:
[1] Rupprecht R, Papadopoulos V, Rammes G, et al. Translocator protein (18 kDa)(TSPO) as a therapeutic target for neurological and psychiatric disorders[J]. Nature reviews Drug discovery, 2010, 9(12): 971-988.
[2] Venneti S, Lopresti B J, Wang G, et al. PK11195 labels activated microglia in Alzheimer's disease and in vivo in a mouse model using PET[J]. Neurobiology of aging, 2009, 30(8): 1217-1226.
[3] Scott G, Mahmud M, Owen D R, et al. Microglial positron emission tomography (PET) imaging in epilepsy: applications, opportunities and pitfalls[J]. Seizure, 2017, 44: 42-47.
[4] Xu J N, Shen D, Mao W D, et al. The effects of PK11195 on the MCF-7 and T47D were associated with the allopregnanolone biosynthesis, which was mediated by Translocator Protein 18 KDa[J]. Cancer Biomarkers, 2016, 17(1): 11-16.
[5] Gao Z W, Huang J B, Lin Q, et al. The effects of PK11195 on meningioma was associated with allopregnanolone biosynthesis, which was mediated by translocator protein 18 kDa[J]. Cancer Biomarkers, 2016, 16(1): 65-69.
[6] Mendonça-Torres M, Roberts S. The translocator protein (TSPO) ligand PK11195 induces apoptosis and cell cycle arrest and sensitizes to chemotherapy treatment in pre-and post-relapse neuroblastoma cell lines[J]. Cancer Biology & Therapy, 2013, 14(4): 319-326.
[7] Ma L, Zhang H, Liu N, et al. TSPO ligand PK11195 alleviates neuroinflammation and beta-amyloid generation induced by systemic LPS administration[J]. Brain research bulletin, 2016, 121: 192-200.
[8] Christensen A, Pike C J. TSPO ligand PK11195 improves Alzheimer-related outcomes in aged female 3xTg-AD mice[J]. Neuroscience letters, 2018, 683: 7-12.
PK 11195是一种异喹啉甲酰胺衍生物，作为非苯二氮䓬类转运蛋白（TSPO）选择性配体[1]。PK 11195可特异性标记中枢神经系统（CNS）中的小胶质细胞，其结合活性在活化的小胶质细胞中显著增强[2]。PK 11195已广泛应用于正电子发射断层扫描（PET）神经成像研究，并在动物模型中作为神经调节剂调控神经功能[3]。
在体外，PK 11195处理72小时可抑制MCF-7和T47D细胞活力，IC50值分别为5.4nM和6.0nM[4]。PK 11195处理72小时抑制IOMM-LEE细胞活力，IC50值为1.505 ± 0.08nM，并能逆转AC-5216促进的allopregnanolone水平升高[5]。50μM的PK 11195处理SMS-KCN细胞24小时可抑制细胞增殖、诱导凋亡并引起G1/S期细胞周期阻滞，同时降低化疗耐药外排泵ABCA3、ABCB1和ABCC1的mRNA表达[6]。
在体内，C57/BL6小鼠连续14天腹腔注射PK 11195（3mg/kg/day）可预防脂多糖（500μg/kg/day；腹腔注射）诱导的认知功能障碍，减轻神经炎症并促进神经类固醇合成[7]。16月龄雌性3xTg-AD小鼠每周腹腔注射PK 11195（3mg/kg/week；持续5周）能改善认知行为表现，并减少可溶性及沉积性β-淀粉样蛋白[8]。
| Cell experiment [1]: | |
Cell lines | MCF-7 cells |
Preparation Method | The MCF-7 cells were cultured in Dulbecco’s modified Eagle’smedium (DMEM) which was supplemented with 10% fetal bovine serum (FBS) in a humidified atmosphere containing 5% CO2 at 37°C. MCF-7 cells were plated at a density of 10,000 cells per well in the 96-well plates and allowed to attach overnight. After 24h, cells were treated with PK 11195 at a concentration gradient of 0, 0.39, 0.78, 1.5625, 3.125, 6.25, 12.5, and 25µg/ml. Cell viability was measured after 72h by the CCK8 assays. |
Reaction Conditions | 0, 0.39, 0.78, 1.5625, 3.125, 6.25, 12.5, and 25µg/ml; 72h |
Applications | PK 11195 treatment reduced the cell viability of MCF-7 cells in a concentration-dependent manner. |
| Animal experiment [2]: | |
Animal models | Female 3xTg-AD mice |
Preparation Method | Sixteen-month-old female 3xTg-AD mice were intraperitoneally injected once a week for 5 weeks with vehicle (1% DMSO in safflower oil; N=6) or 3mg/kg PK 11195. Mice were euthanized 24h after the fifth injection, and brains were rapidly harvested. One hemisphere was fixed by immersion in 4% paraformaldehyde for 48 hours and then stored at 4°C in 0.1M phosphate-buffered saline containing 0.03% sodium azide for immunohistochemical analysis. |
Dosage form | 3mg/kg/week for 5 weeks; i.p. |
Applications | PK 11195 treatment reduced both soluble and deposited β-amyloid in aged female 3xTg-AD mice. |
References: | |
| Cas No. | 85532-75-8 | SDF | |
| 别名 | 1-(2-氯苯基)-N-甲基-N-(1-甲基丙基)-3-异喹啉甲酰胺,RP 52028 | ||
| 化学名 | (R)-N-(sec-butyl)-1-(2-chlorophenyl)-N-methylisoquinoline-3-carboxamide | ||
| Canonical SMILES | ClC1=CC=CC=C1C2=C(C=CC=C3)C3=CC(C(N(C)[C@H](C)CC)=O)=N2 | ||
| 分子式 | C21H21ClN2O | 分子量 | 352.86 |
| 溶解度 | Acetonitrile: 10 mg/ml,Chloroform: 33 mg/ml,Methanol: 16 mg/ml | 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。 |
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| 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 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 2.834 mL | 14.1699 mL | 28.3399 mL |
| 5 mM | 566.8 μL | 2.834 mL | 5.668 mL |
| 10 mM | 283.4 μL | 1.417 mL | 2.834 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
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- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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