MK-6892_DataSheet_MedChemExpress

Inhibitors, Agonists, Screening Libraries

https://www.wendangku.net/doc/a610568776.html, Data Sheet

BIOLOGICAL ACTIVITY:

MK–6892 is a potent, selective, and full agonist for the high affinity nicotinic acid (NA) receptor GPR109A . K i and GTPγS EC 50 of MK–6892 on the Human GPR109A is 4 nM and 16 nM, respectively.

IC50 & 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 EC 50 value of 74nM 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 229μM (~950–fold greater than the in vitro EC 50 determined in mouse NA receptor GTPγS assay, which is 240 nM) in WT mice and 148μM (~620–fold greater than the in vitro EC 50) 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 (EC 50=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].

PROTOCOL (Extracted from published papers and Only for reference)

Animal administration [1]

MK–6892 was orally administered to WT or NA receptor null mice on the same C57Bl/6 genetic background. After 15 min of 100 mpk dosing of NA or 1e to fed WT or NA receptor null mice, the blood levels of MK–6892 at 15 min were 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.

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.

Product Name:

MK–6892Cat. No.:

HY-10680CAS No.:

917910-45-3Molecular Formula:

C 19H 22N 4O 5Molecular Weight:

386.40Target:

GPR109A Pathway:

GPCR/G Protein Solubility:

10 mM in DMSO

Caution: Product has not been fully validated for medical applications. For research use only.

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