| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
Purity: ≥98%
| Targets |
MK-0354 targets GPR109A (also known as niacin receptor 1 or HM74A), a G protein-coupled receptor that is activated by niacin. GPR109A is primarily expressed in adipocytes and immune cells. Activation of GPR109A inhibits adenylyl cyclase, reduces cAMP levels, and activates the antilipolytic pathway, thereby inhibiting lipolysis in adipocytes. By acting as a GPR109A partial agonist, MK-0354 modulates lipid metabolism and has been studied for its potential in treating dyslipidemia.
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| ln Vitro |
In vitro, MK-0354 demonstrates potent agonist activity at human and mouse GPR109A with EC50 values of 1.65 μM and 1.08 μM, respectively. The compound shows no effect on GPR109B, indicating selectivity for GPR109A. As a partial agonist, MK-0354 activates the antilipolytic pathway in adipocytes. The compound's activity has been characterized in receptor binding and functional assays. Specific cellular assay data are not detailed in the available sources.
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| 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] MK-0354 has been evaluated in clinical studies for the treatment of dyslipidemia. The single-dose and multiple-dose pharmacokinetics and pharmacodynamics, as well as tolerability, of MK-0354 were examined in two Phase I studies conducted in healthy male volunteers. The lipid efficacy of MK-0354 was assessed in a Phase II study conducted in male and female patients with dyslipidemia. In vivo, the compound acts as a GPR109A partial agonist to modulate lipid metabolism. |
| Enzyme Assay |
The GPR109A binding assay for MK-0354 involves incubating the compound with membrane preparations from cells expressing human or mouse GPR109A and a radiolabeled niacin ligand. After incubation, bound and free ligands are separated by filtration, and the radioactivity is counted. Functional activity is assessed using a cAMP assay, as GPR109A activation inhibits adenylyl cyclase and reduces cAMP production. Cells expressing GPR109A are seeded in 96-well plates, pre-incubated with varying concentrations of MK-0354, and then stimulated with forskolin to increase cAMP levels. The reduction in cAMP is measured using a cAMP assay kit, and EC50 values are calculated.
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| Cell Assay |
To evaluate the cellular activity of MK-0354, cells expressing the human or mouse GPR109A receptor (such as CHO or HEK293 cells) are seeded in 96-well plates. Cells are pre-incubated with varying concentrations of MK-0354 and then stimulated with forskolin to increase cAMP levels. The intracellular cAMP levels are measured using a cAMP assay kit. The EC50 for reduction of cAMP is calculated. The compound's selectivity can be assessed by testing against GPR109B. In adipocytes, the compound's ability to inhibit lipolysis can be measured by quantifying glycerol release.
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| Animal Protocol |
Specific in vivo animal experiment protocols for MK-0354 are not detailed in the available sources. As a GPR109A agonist, the compound would typically be evaluated in animal models of dyslipidemia. Rodents would be administered MK-0354 orally or intraperitoneally, and plasma lipid levels (such as free fatty acids and triglycerides) would be measured over time. The compound's ability to reduce plasma free fatty acid levels would be assessed. However, specific protocols are not described in the available literature. Clinical studies in humans have been conducted to assess PK, PD, and tolerability.
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| ADME/Pharmacokinetics |
MK-0354 has been evaluated in Phase I and Phase II clinical studies. The single-dose and multiple-dose pharmacokinetics and pharmacodynamics, as well as tolerability, were examined in two Phase I studies in healthy male volunteers. The lipid efficacy was assessed in a Phase II study in patients with dyslipidemia. Specific pharmacokinetic parameters (e.g., Cmax, Tmax, half-life, AUC) are not detailed in the available sources. The compound has a molecular weight of 176.18.
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| Toxicity/Toxicokinetics |
Specific toxicity data for MK-0354 are not provided in the available sources. However, the compound has been evaluated in Phase I and Phase II clinical studies, indicating that its safety profile has been assessed in humans. As a research compound, it is intended for laboratory use only and is not approved for human therapeutic applications. Standard safety precautions should be followed when handling this compound.
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| References |
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| Additional Infomation |
MK-0354 is an oral drug candidate being developed by Merck for the treatment of atherosclerosis and related diseases. It targets the G protein-coupled receptor (GPCR), which has the potential to regulate plasma lipid profiles, including high-density lipoprotein cholesterol (HDL-C, or "good cholesterol"), and its therapeutic effect is similar to that of niacin.
Drug Indications It has been studied for the treatment of atherosclerosis. MK-0354 is a specific GPR109A receptor agonist acting on hGPR109A/mGPR109A with EC50 values of 1.65 μM and 1.08 μM, respectively, with no effect on GPR109B. It is a GPR109A partial agonist that activates the antilipolytic pathway in adipocytes. The compound has been evaluated in Phase I and Phase II clinical studies for dyslipidemia. It has a molecular formula of C7H8N6 and a molecular weight of 176.18. |
| Molecular Formula |
C7H8N6
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| Molecular Weight |
176.17862
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| Exact Mass |
176.081
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| Elemental Analysis |
C, 47.72; H, 4.58; N, 47.70
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| CAS # |
851776-28-8
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| PubChem CID |
11159621
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| Appearance |
Light yellow to khaki solid powder
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| Density |
1.6±0.1 g/cm3
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| Boiling Point |
535.3±60.0 °C at 760 mmHg
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| Flash Point |
273.9±25.8 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.709
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| LogP |
0.67
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
4
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| Rotatable Bond Count |
1
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| Heavy Atom Count |
13
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| Complexity |
197
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| Defined Atom Stereocenter Count |
0
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| SMILES |
N1N=C(C2C3CCCC=3NN=2)NN=1
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| InChi Key |
LTQYSJKGRPGMPO-UHFFFAOYSA-N
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| 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)
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| Chemical Name |
3-(2H-tetrazol-5-yl)-1,4,5,6-tetrahydrocyclopenta[c]pyrazole
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| Synonyms |
MK-0354; MK0354; MK 0354
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| HS Tariff Code |
2934.99.9001
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| 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)
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| Solubility (In Vitro) |
DMSO: ≥ 36 mg/mL (~204.3 mM)
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| 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 |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
| NCT Number | Recruitment | interventions | Conditions | Sponsor/Collaborators | Start Date | Phases |
| NCT00337415 | Terminated | Drug: MK0354 | Dyslipidemia | Merck Sharp & Dohme LLC | May 2006 | Phase 2 |
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