PAANIB-1

PAANIB-1 is a small molecule inhibitor that specifically targets the nuclease activity of **Parthanatos-associated AIF-nuclease (PAAN)**, also known as **Macrophage Migration Inhibitory Factor (MIF)**. Identified through high-throughput screening, PAANIB-1 was developed to block the final execution step of parthanatos, a form of programmed cell death triggered by poly(ADP-ribose) (PAR) polymerase-1 (PARP-1) overactivation. By selectively inhibiting the nuclease function of PAAN/MIF without interfering with its other biological roles, such as its isomerase activity or cytokine functions, PAANIB-1 prevents genomic DNA cleavage and subsequent neuronal death. In preclinical models of Parkinson's disease, including alpha-synuclein preformed fibril (PFF) and MPTP-induced models, PAANIB-1 has demonstrated significant neuroprotective effects, preserving dopaminergic neurons and improving motor function.