nor-NOHA (acetate)

Ki: 0.5 μM for rat liver arginase

nor-NOHA is a potent and reversible inhibitor of rat liver arginase.

L-Arginine is a common substrate for both nitric oxide synthase (NOS) and arginase in the cell. NOS an catalyze the oxidation of arginine to citrulline and NO. Arginase, on the other hand, catalyzes the hydrolysis of arginine into urea and L-ornithine.

In vitro: Previous study found that nor-NOHA could inhibit the proliferation and induce the apoptosis of HepG2 cells. nor-NOHA was also able to decrease the expression levels of Arg1 and MMP-2, increase the expression levels of P53 and ECD as well as the production of NO. In addition, nor-NOHA inhibited the invasion and migration of HepG2 cells. These data indicated that nor-NOHA could induce cell apoptosis and inhibit the ability of invasion and migration of HepG2 cells by inhibiting Arg1 [1].

In vivo: Animal study showd that nor-NOHA treatment could fully restore the aortic response to Ach to that of healthy rats. The results also showed that such beneficial effect was mediated by an increase in NOS activity and EDHF and reduced superoxide anion production. In addition, nor-NOHA could decrease IL-6 and VEGF plasma levels in AIA rats. Whereas, the treatment did not modify arthritis severity in AIA rats [2].

Clinical trial: So far, no clinical study has been conducted.

References:
[1] Li X, Zhu F, He Y, Luo F.  Arginase inhibitor nor-NOHA induces apoptosis and inhibits invasion and migration of HepG2 cells. Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi. 2017 Apr;33(4):477-482.
[2] Prati C, Berthelot A, Kantelip B, Wendling D, Demougeot C.  Treatment with the arginase inhibitor Nw-hydroxy-nor-L-arginine restores endothelial function in rat adjuvant-induced arthritis. Arthritis Res Ther. 2012 May 30;14(3):R130.