Current Medicinal Chemistry - Volume 18, Issue 13, 2011

This special issue of Current Medicinal Chemistry focuses on the chemistry and biology of nicotinamide adenine dinucleotide (NAD and NADP). In recent years, NAD(P)-utilizing enzymes have been extensively investigated and implicated in a wide variety of diseases. Thus, understanding of the role of NAD(P) in medical disorders may lead to potential NAD(P)-based therapeutics. NAD(P) is not only a key component of redox react Read More

A large number of enzymes that use nicotinamide adenine dinucleotide NAD or its phosphorylated form NADP as a cofactor or substrate were found to play an important role in the growth and reproduction of living organisms. NAD(P)-dependent and NAD(P)- utilizing enzymes [NAD(P)-addicted?] have been extensively investigated and implicated in a wide variety of diseases. NAD, generally considered a key component Read More

Inosine 5'-monophosphate dehydrogenase (IMPDH) catalyzes the first committed step of guanosine 5'-monophosphate (GMP) biosynthesis, and thus regulates the guanine nucleotide pool, which in turn governs proliferation. Human IMPDHs are validated targets for immunosuppressive, antiviral and anticancer drugs, but as yet microbial IMPDHs have not been exploited in antimicrobial chemotherapy. Selective inhibitors Read More

Since the discovery in 2000 that the yeast sirtuin called “Sir2” catalyzes NAD+ dependent histone deacetylation, a wave of research has focused on evaluating the biochemical and biological functions of sirtuins. Sirtuins are activated by low calorie diets in numerous organisms and are found throughout biology in species from archaea to humans. There are seven human sirtuin isoforms called SIRT1-SIRT7. The biochemical fu Read More

As members of Class III histone deacetylases (HDACs), sirtuins use stoichiometric nicotinamide adenine dinucleotide (NAD+) to remove the acetyl group from N-acetyl-lysines of histones or non-histone proteins. Sirtuins have been implicated in metabolic diseases, cancer, and neurodegenerative diseases, constituting a promising target for drug discovery. While the early sirtuin inhibitors mimicked NAD+ or subs Read More

Nicotinamide phosphoribosyltransferase (NAMPT) catalyzes the first reversible step in NAD biosynthesis and nicotinamide (NAM) salvage. The enzyme is designed for efficient capture of nicotinamide by coupling of ATP hydrolysis to assist in extraordinary NAM binding affinity and formation of nicotinamide mononucleotide (NMN). NAMPT provides the mechanism to replenish the NAD pool in human metabolism. In addition to Read More

Nicotinamide mononucleotide adenylyltransferease (NMNAT), a rate-limiting enzyme present in all organisms, reversibly catalyzes the important step in the biosynthesis of NAD from ATP and NMN. NAD and NADP are used reversibly in anabolic and catabolic reactions. NAD is necessary for cell survival in oxidative stress and DNA damage. Based on their localization, three different NMNAT's have been recognized, NMNAT-1 (hom Read More

Nicotinamide adenine dinucleotide (NAD+) has a crucial role in many cellular processes, both as a coenzyme for redox reactions and as a substrate to donate ADP-ribose units. Thus, enzymes involved in NAD+ metabolism are attractive targets for drug discovery against a variety of human diseases. Herein we focus on two of them: NMN/NaMN adenylyltransferase (NMNAT) and NAD kinase (NADK). NMNAT is a key enzyme in Read More

As a well-established class, macrolide antibiotics continue to enjoy a remarkable interest within pharmaceutical industry. Several stunning breakthroughs in semi-synthetic study of erythromycin A (EMA) contribute to the important role played by the macrolide class in search for new anti-infectious agents. Earlier structural modifications of EMA to address the issue of acid instability resulted in the first breakthrough in Read More

In many physiopathological conditions, the cell controls its proper dysfunction via activation of the unfolded protein response to restore efficient protein synthesis and folding in the endoplasmic reticulum. However, whether the aim of unfolded protein response is to promote the cell survival, it can also lead to induction of cell death and then affect the cell fate. Recently, endoplasmic reticulum stress appeared to be critical for Read More

Cyclin dependent kinases (CDKs) are a family of proteins involved in the regulation of cell cycle progression and attractive targets in oncology. The regulation of CDKs activities is achieved by their association with cyclin partners and kinases, phosphatases and specific inhibitors. Different CDKs complexes exert their functions at different phases. CDK1 is a master modulator in the initiation and transition process through mitosis o Read More