MK-1903

MK-1903 is an orally active full agonist of GPR109a/HCAR2, with an EC₅₀ of 12.9 nM. MK-1903 activates antilipolytic and vasodilatory pathways, reduces plasma free fatty acid levels, and induces skin flushing. MK-1903 stimulates the expression of HCAR2 protein and regulates the inflammatory response of microglia. MK-1903 prevents the enhanced firing activity of spinal nociceptive neurons. MK-1903 triggers the release of MMP-9 and the formation of NET. MK-1903 can be used in the research of dyslipidemia and neuroinflammation-based central nervous system diseases^[1][2][3]. In Vitro:MK-1903 (0.25-4 μM; 24 h) does not alter the viability of primary rat microglia, and can partially inhibit LPS (HY-D1056)-induced cytotoxicity in these cells^[2].
MK-1903 (1 μM; 24 h) upregulates HCAR2 protein expression in primary rat microglia, and this effect is enhanced when the cells are subsequently treated with LPS^[2].
MK-1903 (1 μM; 24 h) inhibits LPS-induced morphological activation of primary rat microglia, but induces an activated morphology in microglia when used alone^[2].
MK-1903 (1 μM; 24 h) inhibits the LPS-induced upregulation of pro-inflammatory markers (COX-2, IL-1β) and restores the protein expression of the anti-inflammatory factor IL-10 in primary rat microglia^[2].
MK-1903 (1 μM; 24 h) alone increases extracellular IL-10 levels in primary rat microglia, without altering the LPS-induced reduction in extracellular IL-10 levels in these cells^[2].
MK-1903 (1 μM; 24 h) inhibits FKN-induced pro-inflammatory gene expression in mouse BV-2 microglial cells, and upregulates the expression of anti-inflammatory marker genes in these cells when applied alone^[2].
MK-1903 (0.1-10 μM; 10 min) induces the release of MMP-9 from bovine polymorphonuclear leukocytes (PMN)^[3].
MK-1903 (10 μM; 30 min) has no effect on the expression of CD11b or CD47 on the surface of bovine polymorphonuclear neutrophils (PMN)^[3].
MK-1903 (1-10 μM; 60 min) induces the formation of neutrophil extracellular traps (NETs) in bovine polymorphonuclear neutrophils (PMNs), and the NETs colocalize with citrullinated histone H4^[3].
MK-1903 (0.1-10 μM; 2 h) does not induce apoptosis or cell death in bovine polymorphonuclear neutrophils (PMN)^[3]. In Vivo:MK-1903 (0.001-100 mg/kg; p.o.; single dose) produces a dose-dependent, sustained reduction in plasma free fatty acids in fasted male Sprague-Dawley rats^[1].
MK-1903 (1-100 mg/kg; p.o.; single dose) induces a dose-dependent flushing response in anesthetized male C57BL/6 mice, with a ~30% peak increase in ear cutaneous blood flow at the 100 mg/kg oral dose^[1].
MK-1903 (2.62 nmol/5 μL; spinal; single dose) prevents fractalkine-induced spinal nociceptive specific neuron hyperexcitability in healthy male Wistar rats, with no significant changes in NS neuron activity relative to baseline observed post-treatment^[2].