Combined Pharmacophore and Grid-Independent Molecular Descriptors (GRIND) Analysis to Probe 3D Features of Inositol 1,4,5-Trisphosphate Receptor (IP₃R) Inhibitors in Cancer.

ABSTRACT: Inositol 1, 4, 5-trisphosphate receptor (IP₃R)-mediated Ca²⁺ signaling plays a pivotal role in different cellular processes, including cell proliferation and cell death. Remodeling Ca²⁺ signals by targeting the downstream effectors is considered an important hallmark in cancer progression. Despite recent structural analyses, no binding hypothesis for antagonists within the IP₃-binding core (IBC) has been proposed yet. Therefore, to elucidate the 3D structural features of IP₃R modulators, we used combined pharmacoinformatic approaches, including ligand-based pharmacophore models and grid-independent molecular descriptor (GRIND)-based models. Our pharmacophore model illuminates the existence of two hydrogen-bond acceptors (2.62 Å and 4.7

SUBMITTER: Ismatullah H 

PROVIDER: S-EPMC8657927 | biostudies-literature | 2021 Nov

REPOSITORIES: biostudies-literature