Bifendate inhibits cell PARthanatos by activating the MEK/ERK pathway.

ABSTRACT: PARthanatos is a form of programmed cell death increasingly implicated in neurodegenerative diseases and ischemic stroke. Although classical PARP-1 inhibitors can interrupt this pathway, their prolonged use carries a risk of genomic instability. Screening an NMPA-approved compound library identified compound Bifendate (DDB), a clinical used anti-hepatitis drug, as a effective PARthanatos suppressor. In HeLa and SH-SY5Y cells exposed to the PARthanatos inducer MNNG, DDB increased cell viability by approximately 30 % and 70 %, respectively. This inhibitory effect was not attributable to altered protein levels of PARP-1, AIF, or MIF, but to the blockade of AIF translocation from mitochondria to the cytoplasm and nucleus. Mechanistic analyses revealed that DDB treatment can significantly activ

SUBMITTER: Hu AM 

PROVIDER: S-EPMC12830252 | biostudies-literature | 2026 Mar

REPOSITORIES: biostudies-literature