Physicochemical Properties
| Molecular Formula | C49H37F2N3O5S2 |
| Molecular Weight | 849.96 |
| Exact Mass | 849.214 |
| CAS # | 341973-06-6 |
| PubChem CID | 9962675 |
| Appearance | White to off-white solid powder |
| Density | 1.4±0.1 g/cm3 |
| Index of Refraction | 1.721 |
| LogP | 6.28 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 9 |
| Rotatable Bond Count | 12 |
| Heavy Atom Count | 61 |
| Complexity | 1560 |
| Defined Atom Stereocenter Count | 2 |
| 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 |
| 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 |
| HS Tariff Code | 2934.99.9001 |
| 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) |
Biological Activity
| Targets | cPLA2α 4.2 nM (IC50) |
| 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]. |
| 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]. |
| 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. |
| 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. |
| References |
[1]. Pyrrolidine inhibitors of human cytosolic phospholipase A2. Part 2: synthesis of potent and crystallized 4-triphenylmethylthio derivative 'pyrrophenone'. Bioorg Med Chem Lett. 2001 Feb 26;11(4):587-90. [2]. Cytosolic phospholipase A2 alpha regulates cell growth in RET/PTC-transformed thyroid cells. Cancer Res. 2007 Dec 15;67(24):11769-78. [3]. Mechanism of glutamine inhibition of cytosolic phospholipase a2 (cPLA2 ): Evidence of physical interaction between glutamine-Induced mitogen-activated protein kinase phosphatase-1 and cPLA2. Clin Exp Immunol. 2015 Jun;180(3):571-80. |
Solubility Data
| Solubility (In Vitro) | DMSO: 100 mg/mL (117.65 mM) |
| 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 (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *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). 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)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL 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). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently. (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 |