TPPB (α-Amyloid Precursor Protein Modulator)
目录号 : GC10343
TPPB (α-Amyloid Precursor Protein Modulator)是一种苯并内酰胺衍生的、可渗透细胞的蛋白激酶C（PKC）激活剂（Ki = 11.9nM）。
Cas No.:497259-23-1
Sample solution is provided at 25 µL, 10mM.
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TPPB (α-Amyloid Precursor Protein Modulator) is a benzolactam-derived, cell-permeable protein kinase C (PKC) activator (Ki = 11.9nM) [1]. TPPB increases α-secretase activity, leading to increased secretion of sAPPα, while simultaneously decreasing β-secretase (BACE1) expression and the release of Aβ40 fragments [2-3]. TPPB is primarily used to treat Alzheimer's disease [4].
In SH-SY5Y cells, TPPB (0.1-100nM; 3h) induces cell secretion of sAPPα [5]. In PC12 cells, TPPB (0-10μM; 3h) promoted the secretion of sAPPα without affecting the expression of full-length APP [6].
In experimental autoimmune encephalomyelitis (EAE) mice model, TPPB (50nmol/kg; ip; 21d; three days a week) can alleviate the neurological deficits [7].
References:
[1]. Kozikowski A P, Nowak I, Petukhov P A, et al. New amide-bearing benzolactam-based protein kinase C modulators induce enhanced secretion of the amyloid precursor protein metabolite sAPPα[J]. Journal of medicinal chemistry, 2003, 46(3): 364-373.
[2]. Yang H Q, Pan J, Ba M W, et al. New protein kinase C activator regulates amyloid precursor protein processing in vitro by increasing α‐secretase activity[J]. European Journal of Neuroscience, 2007, 26(2): 381-391.
[3]. Hong-Qi Y, Zhi-Kun S, Sheng-Di C. Current advances in the treatment of Alzheimer's disease: focused on considerations targeting Aβ and tau[J]. Translational neurodegeneration, 2012, 1(1): 21.
[4]. Yang H Q, Li X, Yang W M, et al. Neuroprotective Effects of New Protein Kinase C Activator TPPB Against Aβ25–35 Induced Neurotoxicity in PC12 Cells[J]. Neurochemical research, 2012, 37(10): 2213-2221.
[5]. Yi P, Schrott L, Castor T P, et al. Bryostatin-1 vs. TPPB: dose-dependent APP processing and PKC-α,-δ, and-ε isoform activation in SH-SY5Y neuronal cells[J]. Journal of Molecular Neuroscience, 2012, 48(1): 234-244.
[6]. Yang H Q, Pan J, Ba M W, et al. New protein kinase C activator regulates amyloid precursor protein processing in vitro by increasing α‐secretase activity[J]. European Journal of Neuroscience, 2007, 26(2): 381-391.
[7]. Shanmukha S, Godfrey W H, Gharibani P, et al. TPPB modulates PKC activity to attenuate neuroinflammation and ameliorate experimental multiple sclerosis[J]. Frontiers in Cellular Neuroscience, 2024, 18: 1373557.
TPPB (α-Amyloid Precursor Protein Modulator)是一种苯并内酰胺衍生的、可渗透细胞的蛋白激酶C（PKC）激活剂（Ki = 11.9nM） [1]。TPPB可增强α-分泌酶活性，从而增加sAPPα的分泌，同时降低β-分泌酶（BACE1）的表达和Aβ40片段的释放 [2-3]。TPPB主要用于治疗阿尔茨海默病 [4]。
在SH-SY5Y细胞中，TPPB（0.1-100nM；3h）可诱导细胞分泌sAPPα [5]。在PC12细胞中，TPPB（0-10μM；3h）可促进sAPPα的分泌，但不影响全长APP的表达 [6]。
在实验性自身免疫性脑脊髓炎（EAE）小鼠模型中，TPPB（50nmol/kg；ip；21d；每周三天）可以减轻神经功能缺损 [7]。
| Cell experiment [1]: | |
Cell lines | SH-SY5Y cells |
Preparation Method | Cells were grown to confluency in 10 % serum-supplemented medium. Prior to experiments, culture medium was replaced with serum and protein-free (0 %) medium for 2h before drug treatments to remove APP/sAPPα present in FBS and to permit filter concentration of sAPPα. Dilutions of bryostatin-1 or TPPB were added to serum-free culture medium at various concentrations and treatments maintained for 3h, except in time course experiments where several time points up to 24h were taken. Pilot studies showed no change in SH-SY5Y appearance, attachment, or cell density for at least 24h under these conditions. |
Reaction Conditions | 0.1-100nM; 3h |
Applications | TPPB induces cell secretion of sAPPα. |
| Animal experiment [2]: | |
Animal models | Experimental autoimmune encephalomyelitis (EAE) mice model |
Preparation Method | TPPB was dissolved in DMSO to a 1mM stock solution and then diluted to the desired concentration with sterile PBS for animal experiments. Mice were intraperitoneally injected with TPPB (50nmol/kg) or an equal volume of vehicle control three days a week. Mice were randomized and received their first treatment on the day their clinical score reached 1.0 or higher; thereafter, treatment continued three days a week. |
Dosage form | 50nmol/kg; ip; 21d; three days a week |
Applications | TPPB can alleviate the neurological deficits in EAE. |
References: | |
| Cas No. | 497259-23-1 | SDF | |
| 化学名 | (2E,4E)-N-(5-(hydroxymethyl)-2-isopropyl-1-methyl-3-oxo-1,2,3,4,5,6-hexahydrobenzo[e][1,4]diazocin-8-yl)-5-(4-(trifluoromethyl)phenyl)penta-2,4-dienamide | ||
| Canonical SMILES | CC(C1C(NC(CO)CC2=C(C=CC(NC(/C=C/C=C/C3=CC=C(C(F)(F)F)C=C3)=O)=C2)N1C)=O)C | ||
| 分子式 | C27H30F3N3O3 | 分子量 | 501.54 |
| 溶解度 | 25.08mg/mL in DMSO | 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 | 1.9939 mL | 9.9693 mL | 19.9386 mL |
| 5 mM | 398.8 μL | 1.9939 mL | 3.9877 mL |
| 10 mM | 199.4 μL | 996.9 μL | 1.9939 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: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
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