Pirin (PIR)

Pirin is a highly conserved, iron-binding nuclear protein that belongs to the cupin superfamily and functions as both an enzyme (quercetinase, specifically quercetin 2,3-dioxygenase) and a transcriptional co-regulator. Structurally, Pirin features a bicupin fold with an N-terminal Fe²⁺ binding site, crucial for its enzymatic and transcriptional activity. Its enzymatic function is the catalysis of quercetin degradation, producing carbon monoxide as a byproduct. Non-enzymatically, Pirin assists in assembling transcription factors such as NF-κB and Bcl-3, participating in gene regulation, apoptosis, and cell cycle control. Pirin is expressed highly in cardiac and muscle tissue, but is present in most human organs. Pathologically, Pirin has been implicated in cancer development and progression, especially through regulation of telomerase (hTERT) transcription and iron-dependent redox signaling. Drugs affecting Pirin's iron-binding or stability can suppress its transcriptional co-activator role, making Pirin a promising but challenging target for cancer therapeutics—such as in colorectal, lung, and cervical cancers. Pirin's interaction with cellular iron metabolism and redox mechanisms requires careful consideration of therapeutic safety and specificity.

Other names

PirinPIRProbable quercetinaseProbable quercetin 2,3-dioxygenaseIron-binding nuclear proteinQuercetinasePirin (iron-binding nuclear protein)

SP2509 and DFX inhibit Pirin by decreasing iron (Fe³⁺) binding and thus transcriptional co-regulator activity, resulting in suppressed hTERT expression and telomerase activity in cancer cells. Proteolysis-targeting chimeras (PROTACs) targeting Pirin have been explored for its degradation in cancer therapy.