Nitric Oxide Synthase (NOS) Inhibitors

Nitric oxide synthases (NOS) are heme-prosthetic-group-containing enzymes responsible for the synthesis of nitric oxide from L-arginine according to the reaction:

L-arginine + 3/2 NADPH + H+ + 2 O2 = Citrulline + NO+ 3/2 NADP+

NOS enzymes require 5 cofactors which participate in electron flow in the order NADPH > FAD > FMN > heme > Oxygen. In humans, there are three isoforms of NOS enzymes which function in different parts of the body: neuronal nitric oxide synthase (nNOS or NOS-1), endothelial nitric oxide synthase (eNOS or NOS-3) and a cytokine-inducible nitric oxide synthase (iNOS or NOS-2). NOSs work via Calcium-Calmodulin binding.

NO formed by NOS is an important cellular signaling molecule. It helps modulate vascular endothelial cell function by acting as a vasodilator, insulin secretion and tone of airway passages. It is also involved in angiogenesis. nNOS is important in neural development, memory and learning, cardiac function, and peristaltic movements. NO produced by nNOS can function as a neurotransmitter. NO produced by eNOS acts as a part of our defense mechanism against parasites, bacterial infection and tumor growth including autoimmune responses. Bacterial NOS (bNOS) protects bacteria against oxidative damage, many antibiotics and host immune reactions. These are under intense scrutiny in an effort to develop specific bNOS inhibitors for treatment against bacteria. In light of the involvement of NOS enzymes in a multitude of human diseases like heart disease, diabetes, cancer, infections, inflammation, NOS inhibitors are extensively studied and new potent and selective inhibitors targeting each NOS isoform are constantly being investigated. BioVision offers numerous NOS inhibitors acting on all three NOS isoforms.