Description
Title: Identification of Novel Natural Inhibitors of Human 3-Phosphoglycerate Dehydrogenase (PHGDH) for the Treatment of Cancer
Abstract: A cutting-edge method for developing anti-cancer therapeutics is to target the enzymes involved in the serine biosynthesis pathway. Phosphoglycerate dehydrogenase (PHGDH) is a key player in the development of cancer as it is the rate-limiting enzyme that catalyzes the conversion of 3-phosphoglyceric acid (3-PG) into 3-phosphohydroxy pyruvate (3-PPyr) in the first step of the serine synthesis pathway. PHGDH has been identified as a novel target for cancer therapeutics due to reports that it is overexpressed in a variety of cancers. For the purpose of this study, PHGDH inhibitors were found using virtual screening tools. Using the Molegro Virtual Docker (MVD) program, a library of phenolic compounds was docked against the two binding sites of PHGDH. Salvianolic acid I and Chicoric acid were found to be the best binding compounds toward the substrate binding site of PHGDH out of 169 virtually tested compounds. Salvianolic acid C and Schizotenuin F have good binding potential to the cofactor binding site of PHGDH. The top candidates were assessed for various physiochemical and ADMET characteristics, and the results revealed that none of the successful candidates broke the Pfizer Rule and had acceptable ADMET profiles. Furthermore, MGC-803 and SGC-7901, two gastric cancer cell lines that express PHGDH, as well as MCF-7 and MDA-MB2-31, which express PHGDH at low levels, were tested for their anti-cancer potential using a commercially available hit compound called chicoric acid. This showed that chicoric acid has specific cytotoxicity for PHGDH-expressing cancer cell lines. The potential of phenolic compounds has thus been revealed by this research, and they may now represent fresh candidates for the creation of PHGDH inhibitors as anti-cancer drugs.
Keywords: tumor metabolism; PHGDH; phytochemicals; molecular docking; in silico analyses
Paper Quality: SCOPUS / Web of Science Level Research Paper
Subject: Chemistry
Writer Experience: 20+ Years
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