MK-0354 is a novel and potent partial agonist of GPR109a receptor for hGPR109a/ mGPR109a with EC50 of 1.65/1.08 μM, showed no activation of GPR109b. Treatment of atherosclerosis may be possible with it. Plasma FFA was suppressed with little cutaneous flushing after a 7-day course of MK-0354 treatment. But MK-0354 treatment for four weeks did not result in any changes to triglycerides, low-density lipoprotein cholesterol, or high-density lipoprotein cholesterol.
Physicochemical Properties
| Molecular Formula | C7H8N6 |
| Molecular Weight | 176.17862 |
| Exact Mass | 176.081 |
| Elemental Analysis | C, 47.72; H, 4.58; N, 47.70 |
| CAS # | 851776-28-8 |
| PubChem CID | 11159621 |
| Appearance | Light yellow to khaki solid powder |
| Density | 1.6±0.1 g/cm3 |
| Boiling Point | 535.3±60.0 °C at 760 mmHg |
| Flash Point | 273.9±25.8 °C |
| Vapour Pressure | 0.0±1.4 mmHg at 25°C |
| Index of Refraction | 1.709 |
| LogP | 0.67 |
| Hydrogen Bond Donor Count | 2 |
| Hydrogen Bond Acceptor Count | 4 |
| Rotatable Bond Count | 1 |
| Heavy Atom Count | 13 |
| Complexity | 197 |
| Defined Atom Stereocenter Count | 0 |
| SMILES | N1N=C(C2C3CCCC=3NN=2)NN=1 |
| InChi Key | LTQYSJKGRPGMPO-UHFFFAOYSA-N |
| InChi Code | InChI=1S/C7H8N6/c1-2-4-5(3-1)8-9-6(4)7-10-12-13-11-7/h1-3H2,(H,8,9)(H,10,11,12,13) |
| Chemical Name | 3-(2H-tetrazol-5-yl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole |
| Synonyms | MK-0354; MK0354; MK 0354 |
| 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 Vivo |
MK-0354 retained the plasma free fatty acid lowering effects in mice associated with GPR109a agonism, but did not induce vasodilation at the maximum feasible dose. Moreover, preadministration of MK-0354 blocked the flushing effect induced by nicotinic acid but not that induced by PGD2. This profile made MK-0354 a suitable candidate for further study for the treatment of dyslipidemia.[1] Treatment with MK-0354 for 7 days resulted in plasma FFA suppression with minimal cutaneous flushing. However, 4 weeks of treatment with MK-0354 failed to produce changes in high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, or triglycerides.[2] |
| References |
[1]. 3-(1H-Tetrazol-5-yl)-1,4,5,6-tetrahydro-cyclopentapyrazole (MK-0354): A Partial Agonist of the Nicotinic Acid Receptor, G-Protein Coupled Receptor 109a, with Antilipolytic but No Vasodilatory Activity in Mice. J Med Chem. 2008 Aug 28;51(16):5101-8. [2]. Effects of a niacin receptor partial agonist, MK-0354, on plasma free fatty acids, lipids, and cutaneous flushing in humans. J Clin Lipidol. 2008 Oct;2(5):375-383. |
| Additional Infomation |
MK-0354, is an orally administered drug candidate under development by Merck for the treatment of atherosclerosis and related disorders. It targets G protein-coupled receptor, or GPCR, that have the potential to regulate plasma lipid profiles, including HDL, or the good cholesterol, similar to the therapeutic action of niacin. Drug Indication Investigated for use/treatment in atherosclerosis. |
Solubility Data
| Solubility (In Vitro) | DMSO: ≥ 36 mg/mL (~204.3 mM) |
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (14.19 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 25.0 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: ≥ 2.5 mg/mL (14.19 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in 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 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 5.6760 mL | 28.3801 mL | 56.7601 mL | |
| 5 mM | 1.1352 mL | 5.6760 mL | 11.3520 mL | |
| 10 mM | 0.5676 mL | 2.8380 mL | 5.6760 mL |