AZ 482 / AstraZeneca - LARVOL DELTA

Novel anti-Acanthamoeba effects elicited by a repurposed poly (ADP-ribose) polymerase inhibitor AZ9482. (PubMed, Front Cell Infect Microbiol) - "Using a homology model of Acanthamoeba poly (ADP-ribose) polymerases (PARPs), molecular docking of approved drugs revealed three potential inhibitory compounds: olaparib, venadaparib and AZ9482. Analyzing gene expression related to DNA damage repair pathway and the rate of apurinic/apyrimidinic (AP) sites indicated DNA damage efficacy and repair modulation in Acanthamoeba trophozoites following AZ9482 treatment. Collectively, these findings highlight AZ9482, as a structurally unique PARP inhibitor, provides a promising prototype for advancing anti-Acanthamoeba drug research."

Journal • Infectious Disease • Oncology • Targeted Protein Degradation • ANXA5

Modulation of bacterial ADP-ribosyltransferase – fighting against rifamycin resistance and beyond (ACS-Sp 2022) - "b) dose-dependent inhibitory effect of selected inhibitors against M. smegmatis Arr; c) sensitization of M. smegmatis to rifampin by AZ9482. Heatmap of percent inhibition of Msm growth with indicated concentrations of rifampin and AZ9482 (n = 3)"

Infectious Disease • Pulmonary Disease • Respiratory Diseases • Tuberculosis

Structure-guided design and in-cell target profiling of a cell-active target engagement probe for PARP inhibitors. (PubMed, ACS Chem Biol) - "Herein we report the design and application of PARPYnD, the first photoaffinity probe (AfBP) for PARP enzymes based on triple PARP1/2/6 inhibitor AZ9482, which induces multipolar spindle (MPS) formation in breast cancer cells. PARPYnD is a robust tool for profiling PARP1/2, and is used to profile clinical PARP inhibitor olaparib, identifying several novel off-target proteins...These data highlight an intriguing biomolecular disparity between recombinant and endogenous PARP6. PARPYnD provides a new approach to expand our knowledge of the targets of this class of compounds and the mechanisms of action of PARP inhibitors in cancer."

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