PD 146176
(Synonyms: NSC168807) 目录号 : GC12205
PD 146176 是一种有效的选择性网织红细胞 15-LOX-1 抑制剂。
Cas No.:4079-26-9
Sample solution is provided at 25 µL, 10mM.
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PD 146176 is one of the potent and selective inhibitors of reticulocyte 15-LOX-1 [1]. PD 146176 inhibited the activity of h-15-LOX-1 with IC50 value of 16 ± 2.5μM,and Ki value of 3.9 ± 0.6μM [2].
PD 146176 (1 μg ml-1) inhibited the induction of both arginase-1 and mannose receptor mRNA in both rIL-4-treated and RSV-infected WT macrophages, whereas enhancing the induction of COX-2 mRNA [3]. PD 146176 suggested that it causes strong cell cycle arrest in G1 phase. PD 146176 at its IC50, did not show any inhibitory effect on cell directional migration but greatly increased the activity of the caspases in B16F10 cells [4].PD 146176 significantly prevented glutamate-induced cell death in a concentration-dependent manner. PD 146176 fully protected HT-22 cells against glutamate toxicity at a concentration of 0.5 μM and significantly reduced the annexin-V/propidium iodide-positive cells [5].
PD 146176 treated 3xTg mice had significant reductions in Aβ peptide levels, amyloid plaque burden, tau phosphorylation, and insoluble tau deposition in comparison with controls [6,7]. AD model mice in the control group showed a worsening of memory and learning abilities, whereas mice receiving PD 146176 were undistinguishable from wild-type mice [7].
References:
[1]. Orafaie A, Mousavian M, Orafai H, et al. An overview of lipoxygenase inhibitors with approach of in vivo studies[J]. Prostaglandins & Other Lipid Mediators, 2020, 148: 106411.
[2]. Eleftheriadis N, Thee S, Te Biesebeek J, et al. Identification of 6-benzyloxysalicylates as a novel class of inhibitors of 15-lipoxygenase-1[J]. European Journal of Medicinal Chemistry, 2015, 94: 265-275.
[3]. Shirey K A, Lai W, Pletneva L M, et al. Role of the lipoxygenase pathway in RSV-induced alternatively activated macrophages leading to resolution of lung pathology[J]. Mucosal immunology, 2014, 7(3): 549-557.
[4]. Da-Costa-Rocha I, Prieto J M. In vitro effects of selective COX and LOX inhibitors and their combinations with antineoplastic drugs in the mouse melanoma cell line B16F10[J]. International journal of molecular sciences, 2021, 22(12): 6498.
[5]. Tobaben S, Grohm J, Seiler A, et al. Bid-mediated mitochondrial damage is a key mechanism in glutamate-induced oxidative stress and AIF-dependent cell death in immortalized HT-22 hippocampal neurons[J]. Cell Death & Differentiation, 2011, 18(2): 282-292.
[6]. Oddo S, Caccamo A, Shepherd J D, et al. Triple-transgenic model of Alzheimer's disease with plaques and tangles: intracellular Aβ and synaptic dysfunction[J]. Neuron, 2003, 39(3): 409-421.
[7]. Di Meco A, Li J G, Blass B E, et al. 12/15-Lipoxygenase inhibition reverses cognitive impairment, brain amyloidosis, and tau pathology by stimulating autophagy in aged triple transgenic mice[J]. Biological psychiatry, 2017, 81(2): 92-100.
PD 146176 是一种有效的选择性网织红细胞 15-LOX-1 抑制剂[1]。 PD 146176 抑制 h-15-LOX-1 的活性，IC50 值为 16 ± 2.5μM，Ki 值为 3.9 ± 0.6μM [2]。
PD 146176（1 μg ml-1）抑制 rIL-4 处理和 RSV 感染的 WT 巨噬细胞中精氨酸酶-1 和甘露糖受体 mRNA 的诱导，同时增强 COX-2 mRNA 的诱导 [3]. PD 146176 表明它会在 G1 期引起强烈的细胞周期停滞。 IC50 的 PD 146176 对细胞定向迁移没有任何抑制作用，但大大增加了 B16F10 细胞中半胱天冬酶的活性[4]。PD 146176 在一定浓度下显着阻止谷氨酸诱导的细胞死亡-依赖的方式。 PD 146176 在 0.5 μM 浓度下完全保护 HT-22 细胞免受谷氨酸毒性，并显着减少膜联蛋白-V/碘化丙锭阳性细胞[5]。
与对照组相比，PD 146176 处理的 3xTg 小鼠的 Aβ 肽水平、淀粉样斑块负荷、tau 磷酸化和不溶性 tau 沉积显着降低[6,7]。对照组的 AD 模型小鼠表现出记忆和学习能力的恶化，而接受 PD 146176 的小鼠与野生型小鼠没有区别[7]。
| Cell experiment [1]: | |
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Cell lines |
murine melanoma cell line B16F10 |
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Preparation Method |
1 × 104 cells per well were seeded in each well of a 96-well tissue culture plate and left overnight in the incubator. The cells were incubated with PD 146176 for 24, 48, or 72 h similar to the MTT assay. |
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Reaction Conditions |
0.5, 1, 2 , 10, 20, 40µM for 24, 48, 72 hours |
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Applications |
PD 146176 induced cell cycle arrest in G1 phase at 8 h with decrease of cells in S and G2/M phase. The effect on cell morphology is visible observed after 16 h with cells becoming smaller and rounded. |
| Animal experiment [2]: | |
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Animal models |
C57BL/6 mice |
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Preparation Method |
One group was untreated and ate ground rodent chow for 7 days while the experimental group was fed ground rodent chow with the selective PD 146176 added at a concentration to achieve a dose of about 400 mg/kg/day |
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Dosage form |
Fed with diet , 400 mg/kg/day, 7 days |
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Applications |
The mice that were fed PD 146176 lost significantly more weight at 3-5 days after starting dextran sodium sulfate, compared to the corresponding day for the control mice. |
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References: [1]: Da-Costa-Rocha I, Prieto J M. In vitro effects of selective COX and LOX inhibitors and their combinations with antineoplastic drugs in the mouse melanoma cell line B16F10[J]. International journal of molecular sciences, 2021, 22(12): 6498. | |
| Cas No. | 4079-26-9 | SDF | |
| 别名 | NSC168807 | ||
| 化学名 | 6,11-dihydrothiochromeno[4,3-b]indole | ||
| Canonical SMILES | C12=C(C3=CC=CC=C3SC2)NC4=CC=CC=C14 | ||
| 分子式 | C15H11NS | 分子量 | 237.32 |
| 溶解度 | DMF: 10 mg/ml,DMF:PBS (pH 7.2) (1:5): 0.15 mg/ml,DMSO: 10 mg/ml,Ethanol: 2 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 | 4.2137 mL | 21.0686 mL | 42.1372 mL |
| 5 mM | 0.8427 mL | 4.2137 mL | 8.4274 mL |
| 10 mM | 0.4214 mL | 2.1069 mL | 4.2137 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
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet