Pemafibrate |
Catalog No.GC19280
One-Click Copy Product Info
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Pemafibrate (K-877) is an oral peroxisome proliferator-activated receptor (PPAR)-α agonist for the treatment of hyperlipidaemia, EC50 on Gal4hPPARα = 1 nM.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 848259-27-8
Sample solution is provided at 25 µL, 10mM.
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Pemafibrate (K-877) is an oral peroxisome proliferator-activated receptor (PPAR)-α agonist for the treatment of hyperlipidaemia, EC50 on Gal4hPPARα = 1 nM [1].
Pemafibrate (10 µM, 24 h) regulated the expression of several target genes that code for proteins involved in carbohydrate and lipid metabolism, in primary human hepatocytes and the mouse liver [2]. Pemafibrate (50 nM, 24h) activated PPAR-α transcription activity and more effectively than fenofibrate and pirinixic acid (Wy14643) [3].
Pemafibrate (0.001% in MF diets for 1 week) significantly reduced plasma triglyceride and total cholesterol levels, increased plasma HDL cholesterol levels, regulated gene expression related to triglyceride and HDL cholesterol metabolism in the liver, and regulated cholesterol and triglyceride metabolic gene expression in the small intestine in mice [4]. Pemafibrate also promoted cholesterol efflux and reverse cholesterol transport, exerted anti-inflammatory activity, and decreased atherosclerotic lesions [1]. Pemafibrate was more effective than fenofibrate at suppressing the postprandial increase of chylomicrons and the accumulation of chylomicron remnants, thereby attenuating postprandial hypertriglyceridaemia [5].
References:
[1]. Hennuyer N, Duplan I, Paquet C, et al. The novel selective PPARα modulator (SPPARMα) pemafibrate improves dyslipidemia, enhances reverse cholesterol transport and decreases inflammation and atherosclerosis[J]. Atherosclerosis, 2016, 249: 200-208.
[2]. Raza-Iqbal S, Tanaka T, Anai M, et al. Transcriptome analysis of K-877 (a novel selective PPARα modulator (SPPARMα))-regulated genes in primary human hepatocytes and the mouse liver[J]. Journal of atherosclerosis and thrombosis, 2015: 28720.
[3]. Takei K, Han S, Murayama Y, et al. Selective peroxisome proliferator‐activated receptor‐α modulator K‐877 efficiently activates the peroxisome proliferator‐activated receptor‐α pathway and improves lipid metabolism in mice[J]. Journal of Diabetes Investigation, 2017, 8(4): 446-452.
[4]. Takei K, Nakagawa Y, Wang Y, et al. Effects of K-877, a novel selective PPARα modulator, on small intestine contribute to the amelioration of hyperlipidemia in low-density lipoprotein receptor knockout mice[J]. Journal of pharmacological sciences, 2017, 133(4): 214-222.
[5]. Sairyo M, Kobayashi T, Masuda D, et al. A novel selective PPARα modulator (SPPARMα), K-877 (pemafibrate), attenuates postprandial hypertriglyceridemia in mice[J]. Journal of atherosclerosis and thrombosis, 2018, 25(2): 142-152.
| Cell experiment [1]: | |
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Cell lines |
Cryopreserved primary human hepatocytes |
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Preparation Method |
The hepatocyte cultures were maintained at 37⊿ 95% humidity and 5% CO2 for 3 hours and gently replaced with InVitroGRO CP with antibiotics. After 24 hours, the hepatocytes were treated with InVitroGRO CP with antibiotics containing 100 nM and 10 µM of Pemafibrate or 0.01% DMSO as a control. |
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Reaction Conditions |
100 nM and 10 µM for 24 hours |
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Applications |
Pemafibrate treated 11 of the top 20 upregulated genes were involved in carbohydrate and lipid metabolism. |
| Animal experiment [2]: | |
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Animal models |
Female homozygous human apoE2KI mice |
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Preparation Method |
Mice were fed a western diet containing (wt/wt) 0.2% cholesterol and 21% fat for 9 weeks and treated for the last 2 weeks with fenofibrate (250 mg/kg) or pemafibrate (0.1 or 1 mg/kg) or carboxy methyl cellulose (CMC, control). |
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Dosage form |
250mg/kg, 2 weeks, feed with diet. |
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Applications |
Pemafibrate strongly induced ABCA1 (+563%, p < 0.01 at 10 µM) and ABCG1 (+2093% p < 0.001 at 10 µM) mRNA steady-state levels in a dose-dependent manner (+168%, p < 0.05 for ABCA1 and +506%, p < 0.01 for ABCG1) |
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References: [1]: Raza-Iqbal S, Tanaka T, Anai M, et al. Transcriptome analysis of K-877 (a novel selective PPARα modulator (SPPARMα))-regulated genes in primary human hepatocytes and the mouse liver[J]. Journal of atherosclerosis and thrombosis, 2015: 28720. | |
| Cas No. | 848259-27-8 | SDF | |
| Canonical SMILES | CC[C@@H](OC1=CC=CC(CN(C2=NC3=CC=CC=C3O2)CCCOC4=CC=C(OC)C=C4)=C1)C(O)=O | ||
| Formula | C28H30N2O6 | M.Wt | 490.55 |
| Solubility | DMSO : ≥ 100 mg/mL (203.85 mM);Water : < 0.1 mg/mL (insoluble) | 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 | 2.0385 mL | 10.1926 mL | 20.3853 mL |
| 5 mM | 407.7 μL | 2.0385 mL | 4.0771 mL |
| 10 mM | 203.9 μL | 1.0193 mL | 2.0385 mL |
Step 1: Enter information below (Recommended: An additional animal making an allowance for loss during the experiment)
g
μL
Step 2: Enter the in vivo formulation (This is only the calculator, not formulation. Please contact us first if there is no in vivo formulation at the solubility Section.)
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 saline, 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% Appearance: A solid
- COA (Certificate of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Average Rating: 5 (Based on Reviews and 20 reference(s) in Google Scholar.)