Nitric oxide synthase (NOS) catalyzes the conversion of L-arginine to nitric oxide (NO) and citrulline. Methyl-L-NIO (hydrochloride) is a competitive nitric oxide synthase (NOS) inhibitor that competes with L-arginine for the amino acid binding site. It is a more potent inhibitor of nNOS (Ki = 3.0 μM) than eNOS (Ki = 10.0 μM) or iNOS (Ki = 9.5 μM).
Methyl-L-NIO (compound 2d) hydrochloride is a potential selective inhibitor (IC50: 70 μM) of dimethylarginine dimethylaminohydrolase hDDAH. Methyl-L-NIO also has inhibitory activity against NO synthase. The inhibition rates of Methyl-L-NIO on different isoforms of NO synthase at a concentration of 100 μM are 77% (nNOS), 20% (eNOS), and 72% (iNOS) respectively; the inhibition rates at a concentration of 1 mM are 100% (nNOS), 85% (eNOS), 100% (iNOS)[1].
[1] Kotthaus J, et al. Structure–activity relationship of novel and known inhibitors of human dimethylarginine dimethylaminohydrolase-1: alkenyl-amidines as new leads[J]. Bioorganic & medicinal chemistry, 2008, 16(24): 10205-10209.
