A Comprehensive Monograph on Auranofin: From Chrysotherapy to a Modern Polypharmacological Agent

Section 1: Executive Summary

Auranofin (brand name Ridaura®) represents a unique and compelling case study in the lifecycle of a pharmaceutical agent. Initially developed and approved in 1985 as the first orally active gold-containing compound, it was introduced as a novel disease-modifying antirheumatic drug (DMARD) for the treatment of rheumatoid arthritis.[1] Its development marked a significant advancement in chrysotherapy, offering a more convenient and generally better-tolerated alternative to the injectable gold salts of its era.[1] However, the subsequent emergence of more potent and effective DMARDs, such as methotrexate and a host of biologic agents, combined with a significant adverse effect profile associated with its long-term use and commercial decisions by its manufacturer, led to a substantial decline in its clinical application for rheumatological conditions.[5]

In recent years, Auranofin has undergone a remarkable renaissance, driven not by its original indication but by a profound and detailed elucidation of its molecular mechanisms of action. The central discovery that Auranofin is a potent and irreversible inhibitor of the selenoenzyme thioredoxin reductase (TrxR) has repositioned it from a niche antirheumatic agent to a powerful polypharmacological tool with a broad spectrum of potential therapeutic applications.[7] Inhibition of the TrxR/thioredoxin system, a critical cellular antioxidant and redox-regulating pathway, provides a unifying mechanistic rationale for Auranofin's potent activity in diverse pathological contexts. By disrupting cellular redox homeostasis and inducing significant oxidative stress, Auranofin selectively triggers cell death in cells that are highly dependent on this system for survival, a characteristic feature of many cancer cells and pathogenic organisms.[6]