mPGES1-IN-3

mPGES1-IN-3 is a selective, orally active mPGES-1 inhibitor with an IC₅₀ of 8.0 nM for h-mPGES-1 and an IC₅₀ of 10.79 nM for guinea pig mPGES1. mPGES1-IN-3 blocks the conversion of PGH2 (HY-136500) to PGE2 (HY-101952). mPGES1-IN-3 exhibits dose-dependent inhibition of LPS-induced thermal hyperalgesia. mPGES1-IN-3 can be used for research on rheumatoid arthritis^[1]. IC50 & Target:IC50: 8 nM (mPGES-1)^[1] In Vitro:mPGES1-IN-3 (Compound 17d) (10 μM; 60 min) exhibits favorable in vitro ADME properties, including good HWB potency, high metabolic stability across species, minimal CYP inhibition, and high plasma protein binding^[1].
mPGES1-IN-3 (10 μM) exhibits much higher selectivity for mPGES-1 over other prostaglandin synthases and COX enzymes, and has a favorable hERG and off-target safety profile^[1].
mPGES1-IN-3 is a potent inhibitor of guinea pig mPGES-1 and h-mPGES-1, but shows no inhibitory effect on rat or mouse mPGES-1^[1]. In Vivo:mPGES1-IN-3 (10-100 mg/kg; p.o.) exhibits dose-dependent inhibition of LPS-induced thermal hyperalgesia in guinea pigs (ED₅₀ = 36.7 mg/kg)^[1].