Recent Advances in NAMPT Inhibitors: A Novel Immunotherapic Strategy.

摘要: Nicotinamide adenine dinucleotide (NAD) is a cofactor of many enzymatic reactions as well being substrate for number NAD-consuming enzymes (e.g., PARPS, sirtuins, etc). NAD can be synthesized de novo starting from tryptophan, nicotinamide, nicotinic acid, or nicotinamide riboside the diet. On other hand, that liberated by salvaged to re-form NAD. In this former instance, phosphoribosyltransferase (NAMPT) bottleneck enzyme. cells in which salvage pathway predominant, NAMPT, therefore, represents an important controller intracellular concentrations, and consequence energy metabolism. It is, not surprising NAMPT over expressed tumoral cells, take advantage sustain growth rate tumor progression. This has led initiation numerous medicinal chemistry programs develop inhibitors context oncology. More recently, however, it been shown do solely target but also have effect on immune system. To add complexity, enzyme secreted extracellular space acts cytokine mainly through activation Toll like Receptor 4 (TLR4), although clarified yet if only receptor responsible its actions. While specific small molecules developed against form growing evidences possibility form. contribution, most recent will reviewed, together with key elements hypothesis targeting drawbacks so far encountered.