917910-45-3

917910-45-3 structure

Name: MK-6892
Chemical Name: 2-({3-[3-(5-Hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]-2,2-dimeth ylpropanoyl}amino)-1-cyclohexene-1-carboxylic acid
CAS Number: 917910-45-3
Molecular Formula: C₁₉H₂₂N₄O₅
Molecular Weight: 386.40200
Catalog: Signaling Pathways GPCR/G Protein GPR109A
Create Date: 2016-06-02 12:13:59
Modify Date: 2024-01-03 02:44:48
MK-6892 is a potent, selective, and full agonist for the high affinity nicotinic acid (NA) receptor GPR109A. Ki and GTPγS EC50 of MK-6892 on the Human GPR109A is 4 nM and 16 nM, respectively.

Name	2-({3-[3-(5-Hydroxy-2-pyridinyl)-1,2,4-oxadiazol-5-yl]-2,2-dimeth ylpropanoyl}amino)-1-cyclohexene-1-carboxylic acid
Synonyms	MK-6892

Description	MK-6892 is a potent, selective, and full agonist for the high affinity nicotinic acid (NA) receptor GPR109A. Ki and GTPγS EC50 of MK-6892 on the Human GPR109A is 4 nM and 16 nM, respectively.
Related Catalog	Signaling Pathways >> GPCR/G Protein >> GPR109A Research Areas >> Cancer
Target	Ki: 4 nM (GPR109A)[1] EC50: 16 nM (GPR109A)[1]
In Vitro	MK-6892 evokes a potent internalization of GPR109A in U2OS β-arrestin2-RrGFP cells.MK-6892 shows an EC50 value of 74 nM on calcium mobilization assay[2].
In Vivo	MK-6892 is orally administered to WT or nicotinic acid (NA) receptor null mice on the same C57Bl/6 genetic background. After 15 min of 100 mg/kg dosing of MK-6892 to fed WT or NA receptor null mice, the blood levels of MK-6892 at 15 min are 229 μM (~950-fold greater than the in vitro EC50 determined in mouse NA receptor GTPγS assay, which is 240 nM) in WT mice and 148 μM (~620-fold greater than the in vitro EC50) in NA receptor null mice. MK-6892 effectively suppresses plasma FFA in the WT but not in the NA receptor null animals, indicating that the FFA reduction of MK-6892 is NA receptor-dependent. MK-6892 is selected for the studies because of its good PK and activity profiles in these two species (EC50=4.6 μM in the GTPγS assay for the rat NA receptor and 1.3 μM in the GTPγS assay for the dog NA receptor). Despite the significant weaker activity of MK-6892 in rat and dog with respect to that in human, MK-6892 shows good activity in reducing FFA in rat and dog models[1].
References	[1]. Shen HC, et al. Discovery of a biaryl cyclohexene carboxylic acid (MK-6892): a potent and selective high affinity niacin receptor full agonist with reduced flushing profiles in animals as a preclinical candidate. J Med Chem. 2010 Mar 25;53(6):2666-70. [2]. Kim HY, et al. Discovery of 4-(phenyl)thio-1H-pyrazole derivatives as agonists of GPR109A, a high affinity niacin receptor. Arch Pharm Res. 2015 Jun;38(6):1019-32.

Molecular Formula	C₁₉H₂₂N₄O₅
Molecular Weight	386.40200
Exact Mass	386.15900
PSA	141.93000
LogP	3.27510

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