Review of various NAMPT inhibitors for the treatment of cancer

Abstract

Nicotinamide phosphoribosyltransferase (NAMPT) is a rate-limiting enzyme in the NAD salvage pathway of mammalian cells and is overexpressed in numerous types of cancers. These include breast cancer, ovarian cancer, prostate cancer, gastric cancer, colorectal cancer, glioma, and b-cell lymphoma. NAMPT is also known to impact the NAD and NADPH pool. Research has demonstrated that NAMPT can be inhibited. NAMPT inhibitors are diverse anticancer medicines with significant anti-tumor efficacy in ex vivo tumor models. A few notable NAMPT specific inhibitors which have been produced include FK866, CHS828, and OT-82. Despite encouraging preclinical evidence of the potential utility of NAMPT inhibitors in cancer models, early clinical trials have yielded only modest results, necessitating the adaptation of additional tactics to boost efficacy. This paper examines a number of cancer treatment methods which target NAMPT, including the usage of individual inhibitors, pharmacological combinations, dual inhibitors, and ADCs, all of which have demonstrated promising experimental or clinical results. We intend to contribute further ideas regarding the usage and development of NAMPT inhibitors in clinical therapy to advance the field of research on this intriguing target.

Keywords: antibody-drug conjugates; dual inhibitors; individual inhibitors; nicotinamide phosphoribosyltransferase; pharmacological combinations.