ONO-RS-082 is a novel, potent and reversible inhibitor of Ca2+-independent phospholipase A2. At 3.5 µM, it has been shown to inhibit epinephrine-stimulated thromboxane production in human platelets. ONO-RS-082 can also disrupt endosome tubule formation and maintenance of the Golgi complex.
Physicochemical Properties
| Molecular Formula | C21H22NO3CL |
| Molecular Weight | 371.85728 |
| Exact Mass | 371.129 |
| CAS # | 99754-06-0 |
| PubChem CID | 6438389 |
| Appearance | White to off-white solid powder |
| Density | 1.247g/cm3 |
| Boiling Point | 580.5ºC at 760mmHg |
| Flash Point | 304.9ºC |
| Index of Refraction | 1.633 |
| LogP | 5.495 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 3 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 26 |
| Complexity | 486 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | CCCCCC1=CC=C(C=C1)/C=C/C(=O)NC2=C(C=CC(=C2)Cl)C(=O)O |
| InChi Key | MDVFITMPFHDRBZ-JLHYYAGUSA-N |
| InChi Code | InChI=1S/C21H22ClNO3/c1-2-3-4-5-15-6-8-16(9-7-15)10-13-20(24)23-19-14-17(22)11-12-18(19)21(25)26/h6-14H,2-5H2,1H3,(H,23,24)(H,25,26)/b13-10+ |
| Chemical Name | 4-chloro-2-[[(E)-3-(4-pentylphenyl)prop-2-enoyl]amino]benzoic acid |
| 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 |
| 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
| ln Vitro | Polymorphonuclear clear cells (PMNs) generated by P. aeruginosa strain PAO1 cannot migrate transepithelially when exposed to ONO-RS-082 (10 μM), suggesting that PLA2 is essential for this mechanism [3]. |
| ln Vivo | ONO-RS-082 (50 mg/kg/day; prophylactic therapy, days 0 to 21) decreases the development of PH in the MCT-PH model with long-term activation of KCNK3 in vivo [4]. In contrast, short-term KCNK3 activation (curative treatment) in vivo by ONO-RS-082 failed to ameliorate PH symptoms, which was related to the total loss of KCNK3 expression in MCT-PH distribution from 14 to 21 days [4]. |
| Cell Assay |
Cell Viability Assay[3] Cell Types: A549 lung epithelial cell line Tested Concentrations: 10 μM Incubation Duration: 2 hrs (hours) of pretreatment Experimental Results: Completely blocked HXA3-mediated PAO1-induced PMN transepithelial migration. PAO1-induced PGE2 release was largely prevented. |
| Animal Protocol |
Animal/Disease Models: MCT- Pulmonary Hypertension (PH) Rat Model [4] Doses: 50 mg/kg/day Route of Administration: Experimental Results: Long-term reduction in the development of PH in the MCT-PH model. |
| References |
[1]. Activation of phospholipases A and C in human platelets exposed to epinephrine: role of glycoproteins IIb/IIIa and dual role of epinephrine. Proc Natl Acad Sci U S A.1986 Dec;83(23):9197-201. [2]. Effect of phospholipase A2 inhibitors on mouse T lymphocytes. I. Phospholipase A2 inhibitors exert similar immunological activities as glycosylation inhibiting factor. Int Immunol. 1989;1(4):425-33. [3]. Selective eicosanoid-generating capacity of cytoplasmic phospholipase A2 in Pseudomonas aeruginosa-infected epithelial cells. Am J Physiol Lung Cell Mol Physiol. 2011 Feb;300(2):L286-94. [4]. Implication of Potassium Channels in the Pathophysiology of Pulmonary Arterial Hypertension. Biomolecules. 2020 Sep 1;10(9):1261. |
Solubility Data
| Solubility (In Vitro) | DMSO : ~100 mg/mL (~268.92 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: 2.5 mg/mL (6.72 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. 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. Solubility in Formulation 2: 2.5 mg/mL (6.72 mM) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.6892 mL | 13.4459 mL | 26.8918 mL | |
| 5 mM | 0.5378 mL | 2.6892 mL | 5.3784 mL | |
| 10 mM | 0.2689 mL | 1.3446 mL | 2.6892 mL |