Identification of novel PHGDH inhibitors based on computational investigation: an all-in-one combination strategy to develop potential anti-cancer candidates.

ABSTRACT:

Objective

Biological studies have elucidated that phosphoglycerate dehydrogenase (PHGDH) is the rate-limiting enzyme in the serine synthesis pathway in humans that is abnormally expressed in numerous cancers. Inhibition of the PHGDH activity is thought to be an attractive approach for novel anti-cancer therapy. The development of structurally diverse novel PHGDH inhibitors with high efficiency and low toxicity is a promising drug discovery strategy.

Methods

A ligand-based 3D-QSAR pharmacophore model was developed using the HypoGen algorithm methodology of Discovery Studio. The selected pharmacophore model was further validated by test set validation, cost analysis, and Fischer randomization validation and was then used as a 3D query to screen compound libraries with various

SUBMITTER: Xu Y 

PROVIDER: S-EPMC11383787 | biostudies-literature | 2024

REPOSITORIES: biostudies-literature