Background: Poly (ADP-ribosyl) polymerase 1 (PARP1) is important in maintaining genomic
stability, repairing DNA damage, and regulating transcriptional processes. Altered PARP1 activity
is associated with a multitude of pathologies especially cancer. The broad application prospects
of PARP1 inhibitors attract many well-known pharmaceutical companies, which promotes the development
of PARP1 inhibitors.
Objective: Present review aims to introduce PARP1 inhibitors by their structures and try to point out
future development direction of PARP1 inhibitors.
Method: Details regarding the PARP1and PARP1 inhibitors are obtained from PubMed literatures and
Conclusion: The action mode of PARP1 inhibitors developed so far is competing with NAD+ for the
catalytic site of PARP1. Using such inhibitors affects multiple NAD+-dependent enzymatic pathways,
which results in secondary toxic effects. Designing inhibitors targeting other binding sites on the
PARP1 protein is a strategy to bypass this pitfall. Analyzing the structure-activity relationships of
active PARP1 inhibitors described in the patents, we conclude that for the binding activity, amide
group, aromatic ring or heterocyclic ring with rich electronics and heteroatom-substituted in the meta
position of amide group are essential. Big substituents introduced in the heterocyclic ring can enhance
inhibitory activity and improve solubility or other physicochemical properties. Clinical trials of
PARP1 inhibitor were focused on cancer therapies and have achieved remarkable results.