PD 146176
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| رقم الكتالوجGC12205 |
PD 146176 (NSC168807) ، مثبط 15-Lipoxygenase (15-LO) ، يمنع الأرانب الشبكية 15-LO (Ki \u003d 197 نانومتر ، IC50 \u003d 0.54 ميكرومتر).
Products are for research use only. Not for human use. We do not sell to patients.
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.
| 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 | |
| المرادفات | NSC 168807 | ||
| Chemical Name | 6,11-dihydrothiochromeno[4,3-b]indole | ||
| Canonical SMILES | C12=C(C3=CC=CC=C3SC2)NC4=CC=CC=C14 | ||
| Formula | C15H11NS | M.Wt | 237.32 |
| الذوبان | DMF: 10 mg/ml,DMF:PBS (pH 7.2) (1:5): 0.15 mg/ml,DMSO: 10 mg/ml,Ethanol: 2 mg/ml | Storage | Store at -20°C |
| General tips | Please select the appropriate solvent to prepare the stock solution according to the
solubility of the product in different solvents; once the solution is prepared, please store it in
separate packages to avoid product failure caused by repeated freezing and thawing.Storage method
and period of the stock solution: When stored at -80°C, please use it within 6 months; when stored
at -20°C, please use it within 1 month. To increase solubility, heat the tube to 37°C and then oscillate in an ultrasonic bath for some time. |
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| Shipping Condition | Evaluation sample solution: shipped with blue ice. All other sizes available: with RT, or with Blue Ice upon request. | ||
| Prepare stock solution | |||
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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 |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
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μL
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Calculation results:
Working concentration: mg/ml;
Method for preparing DMSO master liquid: mg drug pre-dissolved in μL DMSO ( Master liquid concentration mg/mL, Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug. )
Method for preparing in vivo formulation: Take μL DMSO master liquid, next addμL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O, mix and clarify.
Method for preparing in vivo formulation: Take μL DMSO master liquid, next add μL Corn oil, mix and clarify.
Note: 1. Please make sure the liquid is clear before adding the next solvent.
2. Be sure to add the solvent(s) in order. You must ensure that the solution obtained, in the previous addition, is a clear solution before proceeding to add the next solvent. Physical methods such as vortex, ultrasound or hot water bath can be used to aid dissolving.
3. All of the above co-solvents are available for purchase on the GlpBio website.
Quality Control & SDS
- View current batch:
- Purity: >98.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 27 reference(s) in Google Scholar.)
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