Characterizing the structure-activity relationships of natural products, tanshinones, reveals their mode of action in inhibiting spleen tyrosine kinase.

ABSTRACT: The cytosolic non-receptor protein kinase, spleen tyrosine kinase (SYK), is an attractive drug target in autoimmune, inflammatory disorder, and cancers indications. Here, we employed pharmacophore-based drug screening combined with biochemical assay and molecular dynamics (MD) simulations to identify and characterize inhibitors targeting SYK. The built pharmacophore model, phar-TanI, successfully identified tanshinone (TanI (IC₅₀ = 1.72 μM)) and its analogs (TanIIA (IC₅₀ = 3.2 μM), ST32da (IC₅₀ = 46 μM), and ST32db (IC₅₀ = 51 μM)) which apparently attenuated the activities of SYK in vitro. Additionally, the MD simulations followed by Ligplot analyses revealed that TanI and TanIIA interfered SYK activity through binding deeply into the acti

SUBMITTER: Tung MC 

PROVIDER: S-EPMC8693659 | biostudies-literature | 2021 Jan

REPOSITORIES: biostudies-literature