NAD is a crucial cellular factor that plays multifaceted roles in wide ranging biological processes. Low levels of NAD have been linked to numerous diseases including metabolic disorders, cardiovascular disease, neurodegeneration, and muscle wasting disorders. A novel strategy to boost NAD is to activate nicotinamide phosphoribosyltransferase (NAMPT), the putative rate-limiting step in the NAD salvage pathway. We previously showed that NAMPT activators increase NAD levels in vitro and in vivo. Herein we describe the optimization of our NAMPT activator prototype (SBI-0797812) leading to the identification of 1-(4-((4-chlorophenyl)sulfonyl)phenyl)-3-(oxazol-5-ylmethyl)urea (34) that showed far more potent NAMPT activation and improved oral bioavailability.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1016/j.bmcl.2021.128007 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Maximal Intensity Exercise Induces Adipokine Secretion and Disrupts Prooxidant-Antioxidant Balance in Young Men with Different Body Composition.
Int J Mol Sci
January 2025
Department of Sports Medicine and Human Nutrition, Institute of Biomedical Sciences, Faculty of Physical Education and Sport, University of Physical Education in Kraków, 31-571 Kraków, Poland.
Maximal physical effort induces a disturbance in the body's energy homeostasis and causes oxidative stress. The aim of the study was to determine whether prooxidant-antioxidant balance disturbances and the secretion of adipokines regulating metabolism, induced by maximal intensity exercise, are dependent on body composition in young, healthy, non-obese individuals. We determined changes in the concentration of advanced protein oxidation products (AOPP), markers of oxidative damage to nucleic acids (DNA/RNA/ox), and lipid peroxidation (LPO); catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPx) activity, as well as concentrations of visfatin, leptin, resistin, adiponectin, asprosin, and irisin in the blood before and after maximal intensity exercise in men with above-average muscle mass (NFAT-HLBM), above-average fat mass (HFAT-NLBM), and with average body composition (NFAT-NLBM).
View Article and Find Full Text PDFVisfatin Enhances RANKL-Induced Osteoclastogenesis In Vitro: Synergistic Interactions and Its Role as a Mediator in Osteoclast Differentiation and Activation.
Biomolecules
November 2024
Department of Dental Pharmacology, School of Dentistry, Education and Research Team for Life Science on Dentistry, Pusan National University, Yangsan 50612, Republic of Korea.
Visfatin, an adipokine secreted by various cell types, plays multifaceted pathophysiological roles in inflammatory conditions, including obesity, which is closely associated with osteoclastogenesis, a key process underlying bone loss and increased osteoporosis (OP) risk. However, the role of visfatin in osteoclastogenesis remains controversial. This study was conducted to investigate the effects of visfatin on receptor activator of nuclear factor kappa-B ligand (RANKL)-induced osteoclast differentiation from precursor cells in vitro.
View Article and Find Full Text PDFSomatic Changes of Maternal High-Fat Diet on Offspring-Possible Deleterious Effects of Flavonoids?
Nutrients
November 2024
2nd Department of Obstetrics and Gynecology, "Iuliu Haţieganu" University of Medicine and Pharmacy, 400012 Cluj-Napoca, Romania.
: The rapidly increasing rate of obesity has become an extremely important public health problem, particularly in developed countries. Obesity is associated with a range of health problems, often referred to as the metabolic syndrome. Adipose tissue is now regarded as an endocrine organ responsible for the hormonal secretion of adipokines, which are cytokines involved in various physiological processes.
View Article and Find Full Text PDFBiological production of nicotinamide mononucleotide: a review.
Crit Rev Biotechnol
December 2024
Department of Chemical Engineering, Chungbuk National University, Cheongju, Chungbuk, Republic of Korea.
Nicotinamide mononucleotide (NMN) presents significant therapeutic potential against aging-related conditions, such as Alzheimer's disease, due to its consistent and strong pharmacological effects. Aside from its anti-aging effect, NMN is also an emerging noncanonical cofactor for orthogonal metabolic pathways in the field of biomanufacturing. This has significant advantages in the field of metabolic engineering, allowing cells to produce unnatural chemicals without disrupting the natural cellular processes.
View Article and Find Full Text PDFNAD+ METABOLISM RESTRICTION BOOSTS HIGH-DOSE MELPHALAN EFFICACY IN PATIENTS WITH MULTIPLE MYELOMA.
Blood Adv
December 2024
IRCCS San Martino, Italy.
Elevated levels of the nicotinamide adenine dinucleotide (NAD+)-generating enzyme nicotinamide phosphoribosyltransferase (NAMPT) are a common feature across numerous cancer types. Accordingly, we previously reported pervasive NAD+ dysregulation in Multiple Myeloma (MM) cells in association with upregulated NAMPT expression. Unfortunately, albeit being effective in preclinical models of cancer, NAMPT inhibition has proven ineffective in clinical trials due to the existence of alternative NAD+ production routes utilizing NAD+ precursors other than nicotinamide.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!