Exploration of a Large Virtual Chemical Space: Identification of Potent Inhibitors of Lactate Dehydrogenase-A against Pancreatic Cancer.

ABSTRACT: It is imperative to explore the gigantic available chemical space to identify new scaffolds for drug lead discovery. Identifying potent hits from virtual screening of large chemical databases is challenging and computationally demanding. Rather than the traditional two-dimensional (2D)/three-dimensional (3D) approaches on smaller chemical libraries of a few hundred thousand compounds, we screened a ZINC library of 15 million compounds using multiple computational methods. Here, we present the successful application of a virtual screening methodology that identifies several chemotypes as starting hits against lactate dehydrogenase-A (LDHA). From 29 compounds identified from virtual screening, 17 (58%) showed IC₅₀ values < 63 μM, two showed single-digit micromolar inhibition, and

SUBMITTER: Sharma H 

PROVIDER: S-EPMC9930117 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature