Arginase (ARG) is an enzyme that catalyzes the hydrolysis of L-arginine into L-ornithine and urea as part of the urea cycle. Arginase has two distinct isoforms, arginase I and II. These two isoforms differ in their distribution in different tissues, subcellular localization, and molecular regulation. Arginase activity serves two primary homeostatic functions: first, it eliminates ammonia from the body by producing urea, and second, it produces ornithine, a building block for polyamines and prolines. Ornithine decarboxylase (ODC) generates polyamines that are required for cell proliferation and the control of a number of ion channels. Collagen must be produced, and ornithine aminotransferase (OAT) produces proline.
Arginase I, a cytosolic enzyme with high levels of expression in the liver, is crucial for the hepatic urea cycle. Arginase II, on the other hand, is a mitochondrial enzyme that is widely expressed outside of the liver, with the kidney and prostate being the two main locations. Arginase performs crucial roles in cell growth and repair, as well as defense against NH3 toxicity. In mammals, excessive arginase activity has been linked to disease and dysfunction of the nervous and cardiovascular systems. These disease states might be impacted by two pertinent aspects of this elevated activity. First off, too much arginase activity depletes the L-arginine supply that nitric oxide (NO) synthase needs to produce NO. Second, ornithine toxicity and problems with vascular structure are brought on by excessive ornithine production. Arginase is also a potential therapeutic target for the management of both male and female sexual arousal disorders.
|BEC HCl is a novel and potent Arginase II inhibitor (Ki = 0.31 μM), the binding isslow and competitive.
|Lacto-N-fucopentaose III (LNFP-III)
|Numidargistat (CB1158, INCB01158)
|Numidargistat (CB-1158 B, INCB-01158) is a novel, potent and orally bioavailable immunomodulating agent acting as an arginase inhibitor with anticancer effects.
|Numidargistat 2HCl (CB1158, INCB01158)
|Numidargistat 2HCl (CB-1158 B, INCB-01158; INCB001158) is a novel, potent and orally bioavailable immunomodulating agent acting as an arginase inhibitor with IC50s of 86 nM and 296 nM for recombinant human arginase 1 and recombinant human arginase 2, respectively.