1. Product Overview
U-73122 (CAS 112648-68-7) is a potent, selective, and cell-permeable inhibitor of phosphatidylinositol-specific phospholipase C (PLC), a key enzyme in the phosphoinositide signaling pathway. With the molecular formula C₂₉H₄₀N₂O₃ and a molecular weight of 464.64 g/mol, this complex molecule features an estrone-derived steroid backbone linked via a hexyl chain to a maleimide (pyrrole-2,5-dione) group. U-73122 inhibits agonist-induced PLC activation with IC₅₀ values of 1–2.1 µM in human platelets and neutrophils, and blocks ET-1 and parathyroid hormone-induced Ca²⁺ transients with IC₅₀ = 800 nM and 500 nM, respectively. It is a cornerstone tool compound for dissecting PLC-dependent signal transduction pathways in cell biology and pharmacology research.
2. Key Features and Benefits
• Potent PLC Inhibition: Inhibits agonist-induced PLC activation with IC₅₀ = 1–2.1 µM in human platelets and neutrophils; blocks Ca²⁺ signaling with nM-level potency (IC₅₀ = 50–800 nM depending on pathway).
• High Selectivity: Primarily targets PLC-dependent processes with minimal effect on PLC-independent pathways; U-73343 (sc-201422) is available as a negative control for confirming PLC-specific effects.
• Cell-Permeable: Rapidly crosses cell membranes, enabling intracellular PLC inhibition in intact cells without the need for microinjection or transfection.
• Multi-Pathway Probe: Inhibits PLC, phospholipase A₂ (PLA₂), and 5-lipoxygenase (5-LO), making it a versatile tool for studying interconnected lipid signaling networks.
• Well-Characterized In Vivo: Hundreds of peer-reviewed publications validate its use in platelet aggregation studies, neutrophil adhesion assays, neuroblastoma cell signaling, and T-lymphoma invasion models.
3. Major Applications
• Signal Transduction Research: Used to dissect PLC-mediated phosphoinositide turnover (PIP₂ → IP₃ + DAG) in receptor tyrosine kinase, G-protein coupled receptor (GPCR), and ion channel signaling pathways.
• Platelet & Hemostasis Studies: Inhibits collagen-, thrombin-, ADP-, and arachidonic acid-induced human platelet aggregation (IC₅₀ = 1–5 µM), serving as a key tool for anticoagulation and thrombosis research.
• Calcium Signaling: Employed to block IP₃-mediated Ca²⁺ release from endoplasmic reticulum and investigate store-operated Ca²⁺ entry (SOCE) mechanisms.
• Neurobiology: Used in SK-N-SH neuroblastoma cells to study agonist-induced down-regulation of muscarinic receptors and neuronal signal transduction.
• Immunology & Inflammation: Acts as a potent inhibitor of human polymorphonuclear neutrophil (PMN) adhesion to biological surfaces (IC₅₀ = 50 nM), granule exocytosis, and oxidative burst, making it valuable for inflammation and innate immunity research.
• Cancer Cell Invasion: Reported to abolish T-lymphoma cell invasion into fibroblast monolayers, suggesting applications in metastasis and cell motility studies.
4. Technical Specifications
Item Description
Product Name U-73122 (Phospholipase C Inhibitor)
Synonyms 1-[6-(((8R,9S,13S,14S,17S)-3-Methoxy-13-methyl-7,8,9,11,12,13,14,15,16,17-decahydro-6H-cyclopenta[a]phenanthren-17-yl)amino]hexyl]-1H-pyrrole-2,5-dione; 1-[6-[((17β)-3-Methoxyestra-1,3,5(10)-trien-17-yl]amino]hexyl]-1H-pyrrole-2,5-dione
CAS Number 112648-68-7
Molecular Formula C₂₉H₄₀N₂O₃
Molecular Weight 464.64 g/mol
MDL Number MFCD00893825
PubChem CID 104794
Assay (Purity) ≥95% / ≥98% (HPLC)
Appearance White to off-white crystalline solid or powder
Melting Point Not reported (typical for steroid-maleimide conjugates: 100–180 °C, batch-dependent)
Boiling Point ~617.1 °C (Predicted)
Density ~1.16 g/cm³ (Predicted)
Flash Point ~327 °C
pKa (Predicted) 10.69 ± 0.40
Calculated LogP ~4.0–5.3 (Consensus)
Polar Surface Area (PSA) ~58.6 Ų
Hydrogen Bond Donors 1 (Secondary NH)
Hydrogen Bond Acceptors 4
Rotatable Bonds 9
Solubility Soluble: DMSO (~0.5–1 mg/mL, sonication recommended), Ethanol (~0.7 mg/mL), DMF.
Practically Insoluble:Water (very low aqueous solubility; LogS ≈ -4.8 to -7.1).
Note:May require heating or overnight mixing for complete dissolution.
Spectral Data (Predicted) ¹H NMR (DMSO‑d₆, 400 MHz): δ 0.75–2.80 (m, 20H, steroid skeleton CH/CH₂), 1.30–1.60 (m, 6H, N-CH₂-(CH₂)₄), 2.85 (t, J≈7.0 Hz, 2H, N-CH₂-hexyl), 3.65 (s, 3H, OCH₃), 5.85 (s, 2H, maleimide CH=CH), 6.55–7.15 (m, 3H, aromatic H), 8.50 (br s, 1H, NH).
¹³C NMR (DMSO‑d₆):δ 14.0 (C-18), 23–56 (steroid Cs), 51.0 (OCH₃), 55.0 (N-CH₂), 110–158 (aromatic Cs), 165.0 (maleimide C=O), 170.0 (C-3, ketone).
SMILES O=C(C=C1)N(CCCCCCN[C@@H]2CC[C@@]3([H])[C@]4([H])CCC5=CC(OC)=CC=C5[C@@]4([H])CC[C@]23C)C1=O
InChI Key LUFAORPFSVMJIW-ZRJUGLEFSA-N
Storage (Powder) Room temperature, dark place, inert atmosphere (N₂/Ar); stable ≥12–18 months
Solution Stability DMSO/ethanol solutions unstable over time; reconstitute fresh. Dried aliquots (evaporated under N₂) stable at -20°C for up to 6 months.
HS Code 2933.99.90 / 3822.90.00 (Research Tool)
5. Storage and Handling
• Powder Storage: Store in a tightly sealed container at room temperature (15–30°C) in a dark place under inert atmosphere (N₂ or Ar), protected from light and moisture. Stable for at least 12–18 months from date of purchase.
• Stock Solution — Critical: U-73122 is unstable in DMSO and ethanol over time—solutions that turn pink should be discarded immediately. Best practice: reconstitute in anhydrous DMSO or absolute ethanol freshly before each use. Alternatively, prepare intermediate aliquots in anhydrous chloroform, evaporate to dryness under a stream of nitrogen, and store the dried aliquots at -20°C (stable up to 6 months). Reconstitute dried aliquots in anhydrous DMSO or ethanol immediately before use.
• Working Dilution: Dilute into assay buffer or cell culture medium immediately before use. Final DMSO concentration in assays should not exceed 0.1–0.5% (v/v).
• Handling: Minimize light exposure during all operations. Use amber vials or wrap containers in aluminum foil.
6. Safety Summary (Full SDS Highlights)
• GHS Classification: GHS07 – Warning
• Signal Word: Warning
• Hazard Statements:
• H315: Causes skin irritation.
• H319: Causes serious eye irritation.
• H335: May cause respiratory irritation.
• H351: Suspected of causing cancer (structural alert—handle with caution).
• Precautionary Statements:
• P201: Obtain special instructions before use.
• P261: Avoid breathing dust/mist/vapors. Use only in a well-ventilated area or fume hood.
• 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+P312: IF SWALLOWED: Call a POISON CENTER or physician if you feel unwell.
• 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+P313: IF exposed: Get medical advice/attention.
• P330: Rinse mouth if swallowed.
• P337+P313: If eye irritation persists: Get medical advice/attention.
• P403+P233: Store in a well-ventilated place. Keep container tightly closed.
• P501: Dispose of contents/container in accordance with local, regional, and national regulations.
• First Aid Measures:
• Inhalation: Remove to fresh air. If breathing difficult, administer oxygen and seek medical attention.
• Skin Contact: Immediately wash with plenty of soap and water. Remove contaminated clothing. Seek medical advice if irritation or rash develops.
• Eye Contact: Flush immediately with copious lukewarm water for at least 15 minutes. Remove contact lenses if possible. Seek medical attention.
• Ingestion: Rinse mouth. Do NOT induce vomiting. Give water to drink if conscious. Seek medical advice.
• Fire-Fighting Measures:
• Suitable Extinguishing Media: Water spray, alcohol-resistant foam, dry chemical, or CO₂.
• Special Hazards: Combustion may produce irritating/acrid smoke (CO, NOₓ).
• 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. Keep container closed when not in use. Store at room temperature in a dark place, under inert atmosphere. Keep away from strong oxidizers and heat sources.
• Hazardous Decomposition Products: 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 potentially bioactive and cytotoxic compound.
