Propenyl-L-NIO (hydrochloride)

Propenyl-L-NIO (hydrochloride) (ENIPO) is a potent, selective inhibitor of NOS2 (iNOS). The K_i values for inhibition of NOS2, NOS1 (nNOS), and NOS3 (eNOS) by ENIPO are 17, 10.3 and 58.2 µM, respectively, as determined using initial rate binding kinetics. However, ENIPO is a time-dependent inhibitor that, with longer incubations, demonstrates reversible tight binding inhibition that is selective for NOS2 over NOS1 or NOS3. This selectivity results from NOS2 exhibiting a 4-fold faster binding and 10-fold slower dissociation with ENIPO compared to NOS1. Ki values for ENIPO binding to NOS2 and NOS1 are 0.56 and 6 µM, respectively. Accurate determination of the Ki value of ENIPO for NOS3 has not been determined but is expected to be 50-fold less than NOS2.

Références

1 Bretscher, L.E., Li, H., Poulos, T.L., et al. Structural characterization and kinetics of nitric-oxide synthase inhibition by novel N5-(iminoalkyl)- and N5-(iminoalkenyl)-ornithines. J Biol Chem 278(47) 46789-46797 (2003)