Fiboflapon (also known as AM-803 and GSK2190915) is a novel,orally bioavailable and potent FLAP (5-Lipoxygenase-activating protein) inhibitor with binding IC50 of 2.9 nM. Fiboflapon attenuated the early (0-2 h) and late (4-10 h) asthmatic responses to inhaled allergen compared with placebo. GSK2190915 shows potential as a treatment for patients with asthma. Efficacy was demonstrated for GSK2190915 30 mg compared with placebo in day-time symptom scores and day-time SABA use.
Physicochemical Properties
| Molecular Formula | C38H43N3O4S |
| Molecular Weight | 637.8307 |
| Exact Mass | 637.297 |
| CAS # | 936350-00-4 |
| Related CAS # | Fiboflapon sodium;1196070-26-4 |
| PubChem CID | 44473151 |
| Appearance | White to off-white solid powder |
| LogP | 8.976 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 13 |
| Heavy Atom Count | 46 |
| Complexity | 966 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | DFQGDHBGRSTTHX-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C38H43N3O4S/c1-8-44-34-18-14-28(22-40-34)27-12-10-26(11-13-27)23-41-32-17-16-30(45-24-29-15-9-25(2)21-39-29)19-31(32)35(46-37(3,4)5)33(41)20-38(6,7)36(42)43/h9-19,21-22H,8,20,23-24H2,1-7H3,(H,42,43) |
| Chemical Name | 3-[3-tert-butylsulfanyl-1-[[4-(6-ethoxypyridin-3-yl)phenyl]methyl]-5-[(5-methylpyridin-2-yl)methoxy]indol-2-yl]-2,2-dimethylpropanoic 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 | Fiboflapon (AM-803) showed good pharmacokinetics and preclinical toxicity in dogs and storage. Moreover, fibroflapon (AM-803) shows protracted pharmacokinetics in the bronchoalveolar lavage (BAL) model of cryodont death. Efficacious outcomes [1]. |
| ln Vivo | Fiboflapon (AM-803: 1 mg/kg) has an EC50 of roughly 7 nM and persistently suppresses the production of LTB4 in whole blood when stimulated with an ionophore by >90% for up to 12 hours. Fiboflapon (AM-803) stops the formation of cysteine polystyrene leukotriene (CysLT) and LTB4 in the downstream lungs when they are internally challenged with calcium ionophores, with an ED50 of 0.12 mg/kg and 0.37 mg/kg, respectively. The LTB4 and CysLT mice models showed 86% and 41% inhibition rates, respectively, 16 hours after a single 3 mg/kg dosage. LTB4, CysLT, PBS extravasation, and neutrophil influx caused by peritoneal yeast reverse injection were all dose-dependently decreased by fibroflapon in acute environmental conditioning. And last, Fiboflapon lengthens the time needed for intravenous fatal activating factor (PAF) to sterilize [1]. |
| References |
[1]. 5-Lipoxygenase-activating protein (FLAP) inhibitors. Part 4: development of 3-[3-tert-butylsulfanyl-1-[4-(6-ethoxypyridin-3-yl)benzyl]-5-(5-methylpyridin-2-ylmethoxy)-1H-indol-2-yl]-2,2-dimethylpropionic acid (AM803), a potent, oral, once daily FLAP inhibitor. J Med Chem. 2011 Dec 8;54(23):8013-29. [2]. Pharmacology of AM803, a novel selective five-lipoxygenase-activating protein (FLAP) inhibitor in rodent models of acute inflammation. Eur J Pharmacol. 2010 Aug 25;640(1-3):211-8. |
| Additional Infomation |
Fiboflapon is a phenylpyridine. Drug Indication Investigated for use/treatment in inflammatory disorders (unspecified). Mechanism of Action FLAP (5-Lipoxygenase Activating Protein) is a key component early in the leukotriene pathway, a complex signaling process that exerts control over biological processes, such as inflammation and immunity. Excessive production of leukotrienes exacerbates inflammatory diseases, such as asthma; the FLAP gene has also been linked to a significant increase in the risk of myocardial infarction and stroke. AM803 binds to FLAP, inhibiting the synthesis of leukotrienes that cause inflammation. [Amira Pharmaceuticals Website] |
Solubility Data
| Solubility (In Vitro) | DMSO : ~50 mg/mL (~78.39 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (3.92 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. 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. Solubility in Formulation 2: 10 mg/mL (15.68 mM) in 50% PEG300 50% Saline (add these co-solvents sequentially from left to right, and one by one), suspension solution; with ultrasonication. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.5678 mL | 7.8391 mL | 15.6782 mL | |
| 5 mM | 0.3136 mL | 1.5678 mL | 3.1356 mL | |
| 10 mM | 0.1568 mL | 0.7839 mL | 1.5678 mL |