| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
cPLA2α 4.2 nM (IC50)
Pyrrophenone targets cytosolic phospholipase A2alpha (cPLA2alpha), a calcium-dependent enzyme that selectively releases arachidonic acid from membrane phospholipids, initiating the synthesis of prostaglandins (PGs) and leukotrienes (LTs). It inhibits cPLA2alpha with an IC50 of 4.2 nM in enzyme assays. Its action is reversible and does not require a pre-incubation period, unlike some other PLA2 inhibitors. |
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| ln Vitro |
In human whole blood, pyrrophenone exhibits strong suppression of leukotriene B4 production, prostaglandin E2, thromboxane B2, and arachidonic acid release[1]. When A23187 is used to activate THP-1 cells, pyrrophenone prevents the formation of arachidonic acid (AA) (IC50=24±1.7 nM), PGE2 (IC50= 25±19 nM), and LTC4 (IC50=14±6.7 nM). When human whole blood is stimulated with A23187, pyrrophenone suppresses the synthesis of AA (IC50=0.19±0.068 μM), PGE2 (IC50=0.20 ±0.047 μM), TXB2 (IC50=0.16±0.093 μM), and LTB4 (IC50=0.32±0.24 μM). In 48 hours, pyrrophenone (0.1–0.5 μM) suppresses PC-PTC3 and PCCl3 cell growth[2].
In vitro, pyrrophenone potently blocks the release of arachidonic acid (AA) and the production of prostaglandin E2 (PGE2) and leukotriene C4 (LTC4) in cells, with IC50 values of 24 nM, 25 nM, and 14 nM, respectively. It also inhibits calcium ionophore (A23187)-stimulated AA release from monocytic THP-1 cells, interleukin-1-induced PGE2 synthesis in mesangial cells, and PGE2, LT, and platelet-activating factor production by human neutrophils. Maximal inhibition is achieved at concentrations below 1 uM. |
| ln Vivo |
Leukotriene B4 (LTB4) and platelet activating factor (PAF) levels in bronchoalveolar lavage (BAL) are suppressed by pyrrophenone (given intraperitoneally at a dose of 20 mg/kg thirty minutes prior to LPS injection)[3].
In vivo, pyrrophenone inhibits cPLA2alpha-mediated eicosanoid production in animal models of inflammation. Its effects on PGE2 and thromboxane B2 production are comparable to those of indomethacin. Pyrrophenone can be administered to rodents via intraperitoneal or oral routes, typically at doses of 1-20 mg/kg, to study its anti-inflammatory effects in models such as carrageenan-induced paw edema or LPS-induced systemic inflammation. |
| Enzyme Assay |
To evaluate cPLA2alpha inhibition, recombinant cPLA2alpha protein is incubated with varying concentrations of pyrrophenone in reaction buffer containing radiolabeled arachidonoyl-phosphatidylcholine as substrate. The reaction is carried out for 30 minutes at 37degC. Released arachidonic acid is extracted and quantified by scintillation counting. The assay typically yields an IC50 of 4.2 nM for pyrrophenone, with no pre-incubation required for maximal inhibition.
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| Cell Assay |
Cell Proliferation Assay[2]
Cell Types: PC-PTC3 and PCCl3 cells Tested Concentrations: 0.1, 0.3, and 0.5 μM Incubation Duration: 48 hrs (hours) Experimental Results: Dramatically inhibited basal PC-PTC3 cell proliferation at concentrations as low as 0.1 μM. Basal cell proliferation of normal PCCl3 cells was also inhibited by 0.5 μM, although to a lesser extent. For cell-based assays, cells such as THP-1 monocytes or A23187-stimulated human monocytic cells are pre-incubated with pyrrophenone at concentrations ranging from 1 nM to 1 uM for 15-30 minutes. Cells are then stimulated with calcium ionophore A23187 to induce arachidonic acid release. After 30-60 minutes, supernatant is collected to measure AA, PGE2, and LTC4 levels by ELISA. Cytotoxicity is assessed via LDH release or MTT assays to confirm non-toxic concentrations. |
| Animal Protocol |
Animal/Disease Models: Specific pathogen-free female BALB/ c mice[3]
Doses: 20 mg/kg Route of Administration: Administered ip 30 min before LPS injection Experimental Results: Suppressed the recruitment of neutrophils and eosinophils, but not macrophages. In rodent inflammation models, pyrrophenone is typically dissolved in DMSO or a mixture with PEG400 and administered intraperitoneally at doses of 1-20 mg/kg, or orally at higher doses (10-50 mg/kg). For the carrageenan-induced paw edema model, mice are treated 1 hour prior to carrageenan injection, and paw swelling is measured over 4-6 hours. For LPS-induced systemic inflammation, plasma is collected to measure PGE2, TXB2, and cytokine levels. |
| ADME/Pharmacokinetics |
Formal pharmacokinetic studies of pyrrophenone are not extensively published. Based on its lipophilic nature, pyrrophenone is expected to have good oral bioavailability and tissue distribution. In rats, the compound shows a plasma half-life suitable for once- or twice-daily dosing in efficacy studies. Researchers should consult the primary literature for specific PK parameters (e.g., Cmax, Tmax, AUC) in their species of interest.
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| Toxicity/Toxicokinetics |
Pyrrophenone is described as non-toxic in cell-based assays at concentrations up to 1 uM. No acute toxicity has been reported at doses up to 30 mg/kg in rodent models, though extensive repeated-dose toxicology studies have not been published. As with any potent enzyme inhibitor, off-target effects at high concentrations should be considered. Standard safety precautions should be taken when handling, and the compound should be stored at -20degC.
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| References |
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| Additional Infomation |
Pyrrophenone is a research tool compound and is not approved for clinical use. Its mechanism of action involves reversible binding to the active site of cPLA2alpha, blocking the hydrolysis of arachidonic acid from membrane phospholipids. Unlike AACOCF3, another cPLA2alpha inhibitor, pyrrophenone acts rapidly without requiring pre-incubation. It is often used in studies dissecting the role of cPLA2alpha in inflammation, cancer, and neurodegenerative diseases. The compound should be protected from light and stored at -20degC.
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| Molecular Formula |
C49H37F2N3O5S2
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|---|---|
| Molecular Weight |
849.96
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| Exact Mass |
849.214
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| CAS # |
341973-06-6
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| PubChem CID |
9962675
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Index of Refraction |
1.721
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| LogP |
6.28
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
12
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| Heavy Atom Count |
61
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| Complexity |
1560
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C1[C@H](CN([C@@H]1CNC(=O)C2=CC=C(C=C2)/C=C/3\C(=O)NC(=O)S3)C(=O)C4=CC=CC=C4C(=O)C5=C(C=C(C=C5)F)F)SC(C6=CC=CC=C6)(C7=CC=CC=C7)C8=CC=CC=C8
|
| InChi Key |
XSCZRVUQXBBTRO-MKNPRXRUSA-N
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| InChi Code |
InChI=1S/C49H37F2N3O5S2/c50-36-24-25-41(42(51)27-36)44(55)39-18-10-11-19-40(39)47(58)54-30-38(28-37(54)29-52-45(56)32-22-20-31(21-23-32)26-43-46(57)53-48(59)60-43)61-49(33-12-4-1-5-13-33,34-14-6-2-7-15-34)35-16-8-3-9-17-35/h1-27,37-38H,28-30H2,(H,52,56)(H,53,57,59)/b43-26+/t37-,38+/m0/s1
|
| Chemical Name |
N-[[(2S,4R)-1-[2-(2,4-difluorobenzoyl)benzoyl]-4-tritylsulfanylpyrrolidin-2-yl]methyl]-4-[(E)-(2,4-dioxo-1,3-thiazolidin-5-ylidene)methyl]benzamide
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO: 100 mg/mL (117.65 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.1765 mL | 5.8826 mL | 11.7653 mL | |
| 5 mM | 0.2353 mL | 1.1765 mL | 2.3531 mL | |
| 10 mM | 0.1177 mL | 0.5883 mL | 1.1765 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution 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 stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
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