(-)-U-50488 (hydrochloride)

(-)-U-50488 hydrochloride ((-)-Trans-(1S,2S)-U-50488 hydrochloride) is a selective kappa-opioid receptor (KOR) agonist (b>K_d=2.2 nM) over μ-opioid receptor (MOR) (b>K_d=430 nM). (-)-U-50488 hydrochloride is a more active enantiomer than (+)?trans-(1R,2R) U-50488 (HY-15997A)?or the (±)?trans-racemic mixture U-50488 (HY-15997B). (-)-U-50488 hydrochloride has a potent and sustained anti-HIV effect in fected blood monocyte-derived macrophages (MDM)^[1]. IC50 & Target: Kd: 2.2 nM (kappa-opioid receptor (KOR))
Kd: 430 nM (μ-opioid receptor (MOR))^[1] In Vitro: (-)-U-50488 hydrochloride (1 pM-100 nM; 7 days) exhibits a concentration-dependent inhibition of HIV-1 expression, the maximal inhibition at 10?13 M (approximately 73% suppression) in acutely infected blood monocyte-derived macrophages (MDM)^[2].
(-)-U-50488 hydrochloride (10^-13 M; 7-14 days) (10?13 M) markedly inhibits HIV-1 expression both at 7 and 14 days after infection, it has a sustained inhibitory effect on HIV-1 infection in MDM^[2].
In Vivo: (-)-U-50488 hydrochloride (intraperitoneal?injection?; 5mg/kg; 2 hrs before 4% paraformaldehyde (PFA)) acutely induced pMeCP2-S421 (phosphorylation of the methyl-DNA binding protein MeCP2 at Ser421) and Fos selectively in the nucleus accumbens (NAc) but does not alter MeCP2 levels in any brain region^[3].