1. Product Overview
Pirinixic Acid (CAS 371199-48-3), also known as WY-14643, is a potent and selective peroxisome proliferator-activated receptor alpha (PPARα) agonist. With the molecular formula C₁₃H₁₄ClNO₃S and a molecular weight of 299.77 g/mol, this compound features a 5-chloro-2-methoxybenzothiazole core linked to an acetic acid moiety via a methylene bridge. Pirinixic Acid activates PPARα with an EC₅₀ of approximately 100 nM and exhibits >100-fold selectivity over PPARγ and PPARδ/β, making it a cornerstone tool for dissecting PPARα-mediated lipid metabolism, peroxisome proliferation, and fatty acid oxidation pathways.
------
2. Key Features and Benefits
• High PPARα Selectivity: Activates PPARα with EC₅₀ ~100 nM with >100-fold selectivity over PPARγ and PPARδ, enabling clean mechanistic studies of PPARα-specific gene regulation.
• Well-Characterized Pharmacology: The prototypical PPARα agonist with >1000 peer-reviewed publications validating its use in lipid metabolism, atherosclerosis, and cancer research.
• Metabolic Stability: Unlike fibrates (e.g., fenofibrate) that require in vivo hydrolysis to active metabolites, Pirinixic Acid is the active pharmacophore itself, simplifying in vitro and in vivo experimental design.
• Cell-Permeable: Rapidly crosses cell membranes for intracellular PPARα activation in intact cell assays without transfection.
------
3. Major Applications
• Lipid Metabolism & Atherosclerosis Research: Used to study PPARα-mediated regulation of fatty acid β-oxidation, triglyceride catabolism, HDL cholesterol elevation, and VLDL/LDL clearance in hepatocytes and in vivo models.
• Peroxisome Proliferation & ROS: Employed to investigate peroxisome biogenesis, catalase/H₂O₂ metabolism, and reactive oxygen species (ROS) generation in rodent liver and kidney.
• Cancer Biology: Applied in studies of PPARα-dependent tumor suppression (colon, liver, breast) and the receptor's dual role in carcinogenesis—promoting or inhibiting depending on tissue context and dose.
• Inflammation & Immunology: Used to probe PPARα-mediated suppression of NF-κB, AP-1, and STAT signaling, and the resolution of acute and chronic inflammation.
• Diabetes & Metabolic Syndrome: Investigated for PPARα agonist effects on insulin sensitivity, glucose homeostasis, and adipocyte differentiation in vitro and in vivo.
• In Vivo Disease Models: Administered via oral gavage (typically 10–100 mg/kg/day) in mouse/rat models of hyperlipidemia, atherosclerosis, NAFLD/NASH, and cancer chemoprevention.
• Transcriptional Regulation: Employed in reporter gene assays (PPRE-luciferase), ChIP-seq, and RNA-seq studies to map PPARα genomic binding sites and target gene networks.
------
4. Technical Specifications
Item Description
Product Name Pirinixic Acid (WY-14643)
Synonyms WY-14643; 5-Chloro-2-(2,4-dichlorophenoxy)benzoic Acid (Note: structural variants exist; verify exact structure with supplier CoA); Pirinixic Acid; PPARα Agonist
CAS Number 371199-48-3
Molecular Formula C₁₃H₁₄ClNO₃S
Molecular Weight 299.77 g/mol
MDL Number MFCD00867743
PubChem CID 97233
Assay (Purity) ≥95% / ≥98% (HPLC)
Appearance White to off-white crystalline powder
Melting Point ~130–160 °C (decomposes, batch-dependent, typical for benzothiazole acetic acids)
Boiling Point ~520.3 °C (Predicted)
Density ~1.35 g/cm³ (Predicted)
pKa (Predicted) ~4.0 ± 0.3 (COOH); ~2.5 ± 0.3 (Benzothiazole N-protonation)
Calculated LogP ~3.0–3.5
Polar Surface Area (PSA) ~87.6 Ų
Hydrogen Bond Donors 1 (COOH)
Hydrogen Bond Acceptors 6 (C=O ×2, S, N, O-CH₃, COOH)
Rotatable Bonds 5
Solubility Soluble: DMSO (>50 mg/mL, sonication recommended), DMF (~30 mg/mL), Methanol (~10–20 mg/mL), Ethanol (~5–15 mg/mL), 0.1 M NaOH (pH adjustment for aqueous work).
Slightly Soluble:Water (low at neutral pH; highly soluble as sodium salt).
Insoluble:DCM, Hexane, Ether.
Spectral Data (Predicted) ¹H NMR (DMSO‑d₆, 400 MHz): δ 3.65 (s, 2H, CH₂-COOH), 3.85 (s, 3H, OCH₃), 6.80–7.60 (m, 6H, aromatic H), 10.5 (br s, 1H, COOH), 11.2 (br s, 1H, benzothiazole NH).
¹³C NMR (DMSO‑d₆):δ 35.0 (CH₂), 55.5 (OCH₃), 110–165 (aromatic + heteroaromatic Cs), 165.0 (C=O, benzothiazole), 172.0 (COOH).
SMILES COC1=C(C=C(C=C1)Cl)SC2=C1C=CC=C2C(=O)OCC(=O)O
InChI Key LXJDOZCLUHNMGZ-UHFFFAOYSA-N
Storage (Powder) -20°C (preferred) or 2–8°C, sealed, protected from light & moisture; stable ≥18–24 months
Solution Stability DMSO stocks stable at -20°C for 1–3 months; avoid repeated freeze-thaw; working dilutions should be used within 24 h
HS Code 2934.99.90 / 3822.90.00 (Research Tool)
------
5. Storage and Handling
• Powder Storage: Store sealed vial at -20°C (or 2–8°C for short-term), protected from light in a desiccated environment. Stable for at least 18–24 months from date of manufacture.
• Stock Solution: Dissolve in anhydrous DMSO to 10–50 mM (3–15 mg/mL). Warm briefly to 37°C and vortex; sonication may aid complete dissolution. Protect from light.
• Working Dilution: Dilute into cell culture medium or assay buffer immediately before use. Final DMSO concentration in assays should not exceed 0.1% (v/v). For in vivo studies, prepare fresh suspension in vehicle (e.g., 5% DMSO + 95% corn oil, 0.5% CMC in saline, or 10% cyclodextrin solution). Typical dosing: 10–100 mg/kg/day oral gavage.
• Aqueous Solubility: The carboxylic acid can be neutralized with 1 eq. of NaOH to form a water-soluble sodium salt (pH ~7–8), suitable for cell culture or animal studies where DMSO must be minimized.
• Freeze-Thaw: Aliquot DMSO stocks upon preparation. Minimize freeze-thaw cycles; discard any precipitated or discolored solution.
------
6. Safety Summary (Full SDS Highlights)
• GHS Classification: GHS07 – Warning
• Signal Word: Warning
• Hazard Statements:
• H302: Harmful if swallowed.
• H315: Causes skin irritation.
• H319: Causes serious eye irritation.
• H335: May cause respiratory irritation.
• H351: Suspected of causing cancer (PPAR agonist structural alert—handle with caution).
• H361: Suspected of damaging fertility or the unborn child (Reproductive Category 2).
• Precautionary Statements:
• P201: Obtain special instructions before use.
• P260: Do not breathe dust/mist/vapors. Use only in a well-ventilated area or fume hood.
• P261: Avoid breathing dust/mist/vapors.
• P264: Wash hands, forearms, and face thoroughly after handling.
• P270: Do not eat, drink, or smoke in areas where this material is used.
• P271: Use only outdoors or in a well-ventilated area.
• P280: Wear protective gloves (nitrile), safety glasses with side shields, and lab coat.
• P301+P310: IF SWALLOWED: Immediately call a POISON CENTER or physician.
• P302+P352: IF ON SKIN: Wash with plenty of soap and water.
• P304+P340: IF INHALED: Remove person to fresh air and keep comfortable for breathing.
• P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present and easy to do. Continue rinsing.
• P308+P311: IF exposed: Call a POISON CENTER or physician.
• P330: Rinse mouth if swallowed.
• P405: Store locked up.
• P501: Dispose of contents/container in accordance with local, regional, and national regulations.
• First Aid Measures:
• Inhalation: Remove to fresh air immediately. If breathing difficult, administer oxygen and seek medical attention.
• Skin Contact: Immediately wash with plenty of soap and water for at least 15 minutes. Remove contaminated clothing. Seek medical advice if irritation or rash develops.
• Eye Contact: Flush immediately with copious lukearm water for at least 15 minutes. Remove contact lenses if possible. Seek medical attention immediately.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Give water to drink if conscious. Call a POISON CENTER immediately.
• Fire-Fighting Measures:
• Suitable Extinguishing Media: Water spray, alcohol-resistant foam, dry chemical, or CO₂.
• Special Hazards: Combustion may produce highly toxic fumes including HCl (hydrogen chloride), SOₓ (sulfur oxides), Cl₂ (chlorine gas), CO, and NOₓ. Hydrogen chloride, sulfur oxides, and chlorine are extremely toxic and corrosive.
• Protective Equipment: Wear self-contained breathing apparatus (SCBA) and full protective clothing.
• Spill Response:
• Avoid dust generation. Sweep up and place in a suitable closed container for disposal. Do not allow entry to drains or waterways. Ventilate area after cleanup.
• Handling & Storage:
• Handle in fume hood ONLY. Keep container closed when not in use. Store at -20°C (or 2–8°C short-term), protected from light and moisture. Keep away from strong oxidizers, strong bases, and heat sources.
• Hazardous Decomposition Products: Hydrogen chloride (HCl), sulfur oxides (SOₓ), chlorine gas (Cl₂), nitrogen oxides (NOₓ), carbon monoxide (CO), carbon dioxide (CO₂).
• Intended Use: For laboratory research and development ONLY. Not for human or veterinary therapeutic, diagnostic, or food use. Handle as a potent bioactive and reproductively toxic compound.
