α-Amyloid Precursor Protein Modulator 是一种细胞可渗透的苯并内酰胺衍生蛋白激酶 C (PKC) 激活剂，Ki 为 11.9 nM。
α-Amyloid Precursor Protein Modulator is a benzolactam derived PKC activator.
Protein kinase C (PKC) belongs to a family of protein kinase enzymes involved in phosphorylating serine and threonine of other proteins. The PKC enzymes have been involved in regulating the function of other proteins. Protein kinase C plays an important role in several signal transduction cascades. Protein kinase C has been involved in modulating membrane structure events, mediating immune responses, regulating transcription, learning and memory, and regulating cell growth [2].
α-Amyloid Precursor Protein Modulator activated PKC with the Ki value of 11.9 nM for PKCα that efficiently enhanced non-amyloidogenic α-processing of amyloid precursor protein (APP) even at 100 nM in human fibroblast AG06848. α-Amyloid Precursor Protein Modulator displayed a marked loss of tumor promoting activity [1].
参考文献:
[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] Stabel S, Parker P J.? Protein kinase C[J]. Pharmacology & therapeutics, 1991, 51(1): 71-95.
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Cell experiment: |
24 h after plating 2×104 pheochromocytoma PC12 cells in each well of a 96 well plate, cells are incubated with TPPB at a series of concentration (0.1, 0.5, 1, 5, 10, 20 μM). Twelve to 24 h later, the original media is replaced with media containing MTT at a final concentration of 0.5 g/L for 4 h. Cell viability is evaluated with MTT assays[2]. |
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Animal experiment: |
Mice: Mice are 7 weeks old at the beginning of the treatments and are in the resting phase of the hair cycle. TPPB is applied once or else are applied twice weekly for a total of four applications. Two animals are treated at each dose of compound, and 72 h after the last application, the animals are euthanized. Two portions of treated skin are removed from each animal, fixed in neutral buffered formalin, and stained with hematoxylin and eosin for histological analysis[1]. |
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参考文献: [1]. Kozikowski AP, et al. New amide-bearing benzolactam-based protein kinase C modulators induce enhanced secretion of the amyloid precursor protein metabolite sAPPalpha. J Med Chem. 2003 Jan 30;46(3):364-73. |
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