2. Academic Validation
  3. Discovery of a Potent Nicotinamide Phosphoribosyltransferase Activator for Improving Aging-associated Dysfunctions

Discovery of a Potent Nicotinamide Phosphoribosyltransferase Activator for Improving Aging-associated Dysfunctions

  • J Med Chem. 2024 Feb 17. doi: 10.1021/acs.jmedchem.3c02370.
Sicheng Yang 1,  Donghuan Sun 1,  Ying Wu 1 2,  Shuqiang Chen 1,  Yuan Guo 3,  Jian Li 4,  Guoqiang Dong 1,  Chunquan Sheng 1
Affiliations

Affiliations

  • 1 The Center for Basic Research and Innovation of Medicine and Pharmacy (MOE), School of Pharmacy, Second Military Medical University (Naval Medical University), 325 Guohe Road, Shanghai 200433, China.
  • 2 Department of Clinical Pharmacy, 920th Hospital of Joint Logistics Support Force, Kunming 650032, China.
  • 3 College of Chemistry and Materials Science, Northwest University, Xi'an 710127, China.
  • 4 School of Pharmacy, East China University of Science and Technology, Shanghai 200237, China.
PMID: 38367219 DOI: 10.1021/acs.jmedchem.3c02370
Abstract

Nicotinamide adenine dinucleotide (NAD+) plays a crucial role in the cellular energy metabolism pathway. Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting Enzyme involved in the biosynthesis of NAD+. Herein, a series of new NAMPT activators were designed to increase the NAD+ levels and improve aging-associated dysfunctions. In particular, compound C8 effectively activated NAMPT and promoted the biosynthesis of NAD+. Furthermore, we demonstrated that NAMPT activator C8 possessed excellent antiaging effects both in vitro and in vivo. Activator C8 showed potent activity in delaying aging in senescent HL-7702 cells and extended the lifespan of Caenorhabditis elegans. In a naturally aging mouse model, compound C8 effectively alleviated age-related dysfunctions and markers. Therefore, NAMPT activator C8 represented a promising lead compound for the treatment of age-related diseases.

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