PD146176

产品说明书

Print
Chemical Structure| 4079-26-9 同义名 : NSC168807
CAS号 : 4079-26-9
货号 : A945188
分子式 : C15H11NS
纯度 : 99%+
分子量 : 237.32
MDL号 : MFCD05664738
存储条件：

Pure form Keep in dark place,Sealed in dry,2-8°C

In solvent -20°C:3-6个月-80°C:12个月
溶解度 :

DMSO: 25 mg/mL(105.34 mM)，配合低频超声助溶，注意：DMSO长时间开封后，会吸水并导致溶解能力下降，请避免使用长期开封的DMSO
动物实验配方：
生物活性
描述 Human lipoxygenases (LOXs) are the enzymes participating in the metabolism of the polyunsaturated fatty acids and catalyzing their oxidation to a variety of eicosanoids, which as the secondary signal transducers have a major impact on human homeostasis. They are involved in many diseases such as inflammatory responses, cancers, cardiovascular and kidney diseases, neurodegenerative disorders and metabolic syndrome[1].PD146176 (NSC168807), a 15-Lipoxygenase (15-LO) inhibitor, inhibits rabbit reticulocyte 15-LO (Ki=197 nM, IC50=0.54 μM). PD146176 reverses cognitive impairment, brain amyloidosis, and tau pathology by stimulating autophagy in aged triple transgenic mice[2]. In intact IC21 cells transfected with human 15-LO, PD146176 inhibits 13-HODE production with an IC50 of 0.81 μM[3]. PD146176 (80 mg/kg; Chowing; 12 weeks) reverses cognitive impairment, brain amyloidosis, and Tau pathology by stimulating autophagy in aged triple transgenic mice[4]. Compared with mice receiving placebo, the group treated with PD146176 manifested a significant improvement of their memory deficits. The same animals had a significant reduction in Aβ levels and deposition, which was secondary to a decrease in the β-secretase pathway. In addition, while total tau-soluble levels were unchanged for both groups, PD146176-treated mice had a significant reduction in its phosphorylation state and insoluble fraction, which specifically associated with decrease in stress-activated protein kinase/c-Jun N-terminal kinase activity[5].
实验方案
1mg 5mg 10mg

1 mM

5 mM

10 mM

4.21mL

0.84mL

0.42mL

21.07mL

4.21mL

2.11mL

42.14mL

8.43mL

4.21mL
参考文献

[1] E Skrzypczak-Jankun,et al. Human lipoxygenase: developments in its structure, function, relevance to diseases and challenges in drug development. Curr Med Chem. 2012;19(30):5122-7.

[2] Sendobry SM, et al. Attenuation of diet-induced atherosclerosis in rabbits with a highly selective 15-lipoxygenase inhibitor lacking significant antioxidant properties. Br J Pharmacol. 1997;120(7):1199-1206.

[3] Bocan TM, et al. A specific 15-lipoxygenase inhibitor limits the progression and monocyte-macrophage enrichment of hypercholesterolemia-induced atherosclerosis in the rabbit [published correction appears in Atherosclerosis 1998 Jul;139(1):201]. Atherosclerosis. 1998;136(2):203-216.

[4] Di Meco A, et al. 12/15-Lipoxygenase Inhibition Reverses Cognitive Impairment, Brain Amyloidosis, and Tau Pathology by Stimulating Autophagy in Aged Triple Transgenic Mice. Biol Psychiatry. 2017;81(2):92-100.

[5] J Chu,et al. Pharmacologic blockade of 12/15-lipoxygenase ameliorates memory deficits, Aβ and tau neuropathology in the triple-transgenic mice. Mol Psychiatry. 2015 Nov;20(11):1329-38.