GSK2018682 is a novel and potent agonist for S1P1 and S1P5 receptor (sphingosine 1 phosphate receptor) with pEC50s of 7.7 and 7.2, respectively, and it has no agonist activity towards human S1P2, S1P3, or S1P4. GSK2018682 is employed in multiple sclerosis research. Acute, brief, and asymptomatic drops in blood pressure and heart rate were caused by GSK2018682. Absolute lymphocyte count (ALC) and all tested subsets showed dose-dependent decreases to varying degrees, with a nadir of more than 70% reduction from baseline. Major pharmacokinetic parameters did not differ between the fed and fasted subjects or the three GSK2018682 formulations. On the other hand, after dosage in the fed state, the degree of bradycardia decreased. Furthermore, exercise produced a strong rise in heart rate up to 6 mg in subjects with bradycardia after RD of GSK2018682, indicating potential physiological ways to lessen the severity of S1P-mediated bradycardia and the ensuing AV-block.
Physicochemical Properties
| Molecular Formula | C22H21CLN4O4 |
| Molecular Weight | 440.879544019699 |
| Exact Mass | 440.13 |
| Elemental Analysis | C, 59.93; H, 4.80; Cl, 8.04; N, 12.71; O, 14.52 |
| CAS # | 1034688-30-6 |
| Related CAS # | 1034687-52-9 (HCl); 1034688-30-6 |
| PubChem CID | 24988201 |
| Appearance | White to off-white solid powder |
| LogP | 4 |
| Hydrogen Bond Donor Count | 1 |
| Hydrogen Bond Acceptor Count | 7 |
| Rotatable Bond Count | 8 |
| Heavy Atom Count | 31 |
| Complexity | 612 |
| Defined Atom Stereocenter Count | 0 |
| InChi Key | NFIGDBFIDKDNIG-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C22H21ClN4O4/c1-13(2)30-22-17(23)11-14(12-24-22)21-25-20(26-31-21)16-5-3-6-18-15(16)8-10-27(18)9-4-7-19(28)29/h3,5-6,8,10-13H,4,7,9H2,1-2H3,(H,28,29) |
| Chemical Name | 4-[4-[5-(5-chloro-6-propan-2-yloxypyridin-3-yl)-1,2,4-oxadiazol-3-yl]indol-1-yl]butanoic acid |
| Synonyms | GSK-2018682; GSK 2018682; GSK2018682 |
| 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
| Targets | S1P1 receptor ( pEC50 = 7.7 ); S1P5 receptor ( pEC50 = 7.2 ) |
| ln Vitro | GSK2018682 is an agonist at the S1P1 and S1P5 receptors with pEC50s of 7.7 and 7.2, respectively, and has no agonist activity against human S1P2, S1P3 or S1P4 [1]. |
| References |
[1]. Safety, pharmacokinetics, pharmacodynamics, and bioavailability of GSK2018682, a sphingosine-1-phosphate receptor modulator, in healthy volunteers. Clin Pharmacol Drug Dev. 2014 May;3(3):170-8. |
| Additional Infomation | GSK2018682 has been investigated for the treatment of Multiple Sclerosis, Relapsing-Remitting. |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 125 mg/mL (~283.5 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (4.72 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: 2.08 mg/mL (4.72 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 ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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 3: ≥ 2.08 mg/mL (4.72 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 20.8 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 | 2.2682 mL | 11.3410 mL | 22.6819 mL | |
| 5 mM | 0.4536 mL | 2.2682 mL | 4.5364 mL | |
| 10 mM | 0.2268 mL | 1.1341 mL | 2.2682 mL |