WY-14643 (Pirinixic Acid) (Synonyms: NSC 310038, Pirinixic Acid) |
| Katalog-Nr.GC14403 |
WY-14643 (Pirinixic Acid) is a highly potent and selective agonist of the peroxisome proliferator-activated receptor alpha(PPARα), exhibiting an EC50 of 0.63μM for mouse PPARα receptors and an EC50 of 5μM for human PPARα receptors.
Products are for research use only. Not for human use. We do not sell to patients.
Cas No.: 50892-23-4
Sample solution is provided at 25 µL, 10mM.
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WY-14643 (Pirinixic Acid) is a highly potent and selective agonist of the peroxisome proliferator-activated receptor alpha(PPARα), exhibiting an EC50 of 0.63μM for mouse PPARα receptors and an EC50 of 5μM for human PPARα receptors[1].PPARα is a ligand-activated transcription factor that plays a crucial role in lipid metabolism across various tissues and is associated with several diseases, including metabolic syndrome, Alzheimer’s disease, and cardiovascular diseases[2]. WY-14643 (Pirinixic Acid) is a potent antihypercholesterolemic agent that interacts with the PPARα receptor, inducing conformational changes that facilitate heterodimerization with the retinoid X receptor (RXR). This heterodimer then binds to specific response elements in target gene promoters, leading to the activation of transcription[3,4].
Treatment of MCF-7 cells with WY-14643 (30–300μM) led to an increased expression of human cytochrome P450 1B1 (CYP1B1) protein compared to the untreated group, which is implicated in the initiation and progression of breast cancer[5]. Treatment of TCL-1 cells with WY-14643 (0.05–0.2mM) significantly enhanced the activity of catalase (catalase) and increased progesterone secretion at low concentrations, while treatment with higher concentrations reduced the secretion of human chorionic gonadotropin (hCG) and suppressed cell proliferation, suggesting that WY-14643 can modulate trophoblast cell metabolism and function[6].
WY-14643 (5mg/kg or 10mg/kg, 7d) administered via intraperitoneal injection was able to reduce lipopolysaccharide (LPS)-induced depressive-like behaviors in mice and improve anhedonia, demonstrating its potential as an effective antidepressant[7]. WY-14643 (60mg/kg, 30min) administered via intraperitoneal injection prior to traumatic brain injury (TBI) significantly decreased brain water content in mice, alleviating cerebral edema. These results suggest that WY-14643 has a protective effect on blood-brain barrier function following TBI[8].
References:
[1] Willson T M, Brown P J, Sternbach D D, et al., The PPARs: From Orphan Receptors to Drug Discovery, Journal of Medicinal Chemistry[J]. 2000, 43: 527-550.
[2] Lin Y, Wang Y, Li P F, PPARα: An emerging target of metabolic syndrome, neurodegenerative and cardiovascular diseases, Front Endocrinol (Lausanne)[J]. 2022, 13: 1074911.
[3] Santilli A A, Scotese A C, Tomarelli R M, A potent antihypercholesterolemic agent: [4-chloro-6-(2,3-xylidino)-2-pyrimidinylthio]acetic acid (Wy-14643), Experientia[J]. 1974, 30: 1110-1111
[4] Forman B M, Chen J, Evans R M, Hypolipidemic drugs, polyunsaturated fatty acids, and eicosanoids are ligands for peroxisome proliferator-activated receptors alpha and delta, Proc Natl Acad Sci U S A[J]. 1997, 94: 4312-4317.
[5] Hwang Y P, Won S S, Jin S W, et al., WY-14643 Regulates CYP1B1 Expression through Peroxisome Proliferator-Activated Receptor α-Mediated Signaling in Human Breast Cancer Cells, Int J Mol Sci[J]. 2019, 20: 5928.
[6] Hashimoto F, Morita M, Iwasaki K, et al., Effects of WY-14643 on Peroxisomal Enzyme Activity and Hormone Secretion in Immortalized Human Trophoblast Cells, Biological and Pharmaceutical Bulletin[J]. 2009, 32: 1278-1282.
[7] Yang R, Wang P, Chen Z, et al., WY-14643, a selective agonist of peroxisome proliferator-activated receptor-α, ameliorates lipopolysaccharide-induced depressive-like behaviors by preventing neuroinflammation and oxido-nitrosative stress in mice, Pharmacol Biochem Behav[J]. 2017, 153: 97-104.
[8] Neuhaus W, Krämer T, Neuhoff A, et al., Multifaceted Mechanisms of WY-14643 to Stabilize the Blood-Brain Barrier in a Model of Traumatic Brain Injury, Frontiers in Molecular Neuroscience[J]. 2017, 10: 149.
| Cell experiment [1]: | |
Cell lines | MCF-7 cells |
Preparation Method | MCF-7 cells were seeded at a density of 4×104 cells per 500μL in 48-well plates. After incubation for 24h, the growth medium was replaced with serum-free medium and the cells were treated with WY-14643 (30–300μM) or an equal volume of dimethyl sulfoxide for 24h at 37℃. Culture supernatants were subjected to analysis using the lactate dehydrogenase assay and the absorbance at 490nm was measured using a microplate reader. Cell viability was determined using the MTT assay.After treatment, MCF-7 cells were lysed in lysis buffer (120mM NaCl, 40mM Tris[pH 8.0], and 0.1% nonidet P-40) on ice for 30min and centrifuged at 12,000rpm for 20min. Supernatants were collected and protein concentrations were measured using a protein assay kit. Aliquots of the lysates (50μg protein) were boiled for 5min andresolved by using 10% sodium dodecyl sulfate–polyacrylamide gel electrophoresis. The proteins were transferred to polyvinylidene difluoride membranes and incubated with the appropriate primary antibodies. The membranes were incubated with the secondary anti-mouse or anti-rabbit antibody. Finally, the protein bands were detected using an enhanced chemiluminescence western blotting detection kit. |
Reaction Conditions | 30–300μM; 24h |
Applications | WY-14643 enhances the expression of CYP1B1 through a PPARα-dependent mechanism. |
| Animal experiment [2]: | |
Animal models | Traumatic brain injury (TBI) mice |
Preparation Method | WY-14643(60mg/kg, i.p.) or vehicle was administered 30min before Controlled Cortical Impact (CCI). Male C57Bl6/N mice were anesthetized with 5mg/kg midazolam, 0.05mg/kg fentanyl, and 0.5mg/kg medetomidine intraperitoneally. Rectal temperature was maintained at 37℃ with a thermostatically regulated, feedback-controlled heating pad. The cranium was fixed in a stereotactical frame, a craniotomy was generated between lambdoid, sagittal and coronal sutures with a saline cooled high speed drill. The trauma was induced with an electromagnetic cortical impact device diameter of the impactor tip: 3mm; impact velocity: 6m/sec; impact duration: 200ms, and displacement: 1.5mm. The craniotomy was closed with the initially removed bone flap using conventional tissue glue. The skin was carefully closed with four single button sutures, anaesthesia antagonized (0.5mg/kg Flumazenil, and 2.5mg/kg Atipamezole hydrochloride, i.p.) and the animals were transferred back into their cages. The animals were placed for 1.5h in a neonatal incubator with controlled air temperature (35℃) and ambient humidity (35%) to maintain constant body temperature and avoid hypothermia. The animals were reanaesthetized and killed by cervical dislocation. For the quantification of brain water content and further investigations the cerebellum was separated and the hemispheres were cut along the interhemispheric plane slightly. Both hemispheres were separated again in the middle of the contusion area and weighed to assess their wet weight. One half of each hemisphere was dried in a vacuum-centrifuge for 48h at 39℃ to determine the dry weight. |
Dosage form | 60mg/kg for 30min; i.p. |
Applications | Treatment of WY-14643 significantly protected against radiocontrast nephropathy. |
References: | |
| Cas No. | 50892-23-4 | SDF | |
| Überlieferungen | NSC 310038, Pirinixic Acid | ||
| Chemical Name | 2-[4-chloro-6-(2,3-dimethylanilino)pyrimidin-2-yl]sulfanylacetic acid | ||
| Canonical SMILES | CC1=C(C(=CC=C1)NC2=CC(=NC(=N2)SCC(=O)O)Cl)C | ||
| Formula | C14H14ClN3O2S | M.Wt | 323.8 |
| Löslichkeit | ≥ 16.2 mg/mL in DMSO, ≥ 48.8 mg/mL in EtOH with ultrasonic | 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 | |||
|
1 mg | 5 mg | 10 mg |
| 1 mM | 3.0883 mL | 15.4416 mL | 30.8833 mL |
| 5 mM | 617.7 μL | 3.0883 mL | 6.1767 mL |
| 10 mM | 308.8 μL | 1.5442 mL | 3.0883 mL |
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Quality Control & SDS
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- Purity: >98.00%
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Average Rating: 5 (Based on Reviews and 30 reference(s) in Google Scholar.)
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