MK-0354
Cat. No: CDIA-0465
CAS. No.: 851776-28-8
Size: 5 mg
Product Details |
Formula |
C7H8N6 |
Molecular Weight |
176.18 |
Appearance |
Solid |
Purity |
99.21% |
Smiles String |
C12=C(CCC2)C(C3=NN=NN3)=NN1 |
Storage & Handling |
Shipping |
Room temperature. |
Storage Powder |
-20 °C/3 years, 4 °C/2 years |
Description
MK-0354 is a partial agonist of GPR109a receptor, for hGPR109a/ mGPR109a with EC50 of 1.65/1.08 μM, showed no activation of GPR109b.
IC50 value: 1.65 μM (EC50, for hGPR109a), 1.08 μM (EC50, for mGPR109a)
Target: GPR109a
in vitro: MK-0354 demonstrated clear and statistically significant partial agonism in the cAMP assays for both the mouse and human receptors with efficacy approximately 60-70% of that of either nicotinic acid or β-hydroxy butyrate, a putative physiologically relevant ligand for hGPR109a, in the same assay platform. In addition, MK-0354 showed no activation of GPR109b in the cAMP assay at any concentration up to 100 μM. Following these interesting observations, we then prepared a number of other 5,5-fused pyrazoles analogous to those that showed receptor activity in our earlier studies. MK-0354 appeared to be somewhat unique among the members of the pyrazole tetrazole series in having reasonable receptor activity.
in 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. MK-0354 is a GPR109A partial agonist that activates the antilipolytic pathway in adipocytes. 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.
! For research use only. Not intended for any clinical use.
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