MK-6892

本公司产品仅用于科研实验，不得用于人体或动物的临床与诊断

MK-6892 是高亲和力烟酸受体 GPR109A 的选择性完全激动剂（Ki：4 nM；GTPγS EC50：16 nM）。MK-6892 在 U2OS β-arrestin2-RrGFP 细胞中引起 GPR109A 的有效内化。MK -6892 在钙动员测定中显示 EC50 值为 74 nM。

MK-6892 is a selective and full agonist for the high-affinity nicotinic acid receptor GPR109A (Ki: 4 nM; GTPγS EC50: 16 nM).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.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 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.

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.

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Cell Cycle/DNA Damage

GPR

GPR109A

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917910-45-3

386.4

C19H22N4O5

>98% (HPLC)

DMSO:50 mg/mL (129.40 mM; Need ultrasonic)

O=C(C1=C(NC(C(C)(C)CC2=NC(C3=NC=C(O)C=C3)=NO2)=O)CCCC1)O

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(-20℃)

With Ice Pack

≥ 2 years