Fungal metabolites represent an underutilized
resource in the development
of novel anticancer drugs. This review will focus on the promising
fungal nephrotoxin orellanine, found in mushrooms includingCortinarius orellanus(Fools webcap). Emphasis will be placed
on its historical significance, structural features, and associated
toxicomechanics. Chromatographic methods for analysis of the compound
and its metabolites, its synthesis, and chemotherapeutic potential
are also discussed. Although orellanine’s exceptional selectivity
for proximal tubular cells is well documented, the mechanics of its
toxicity in kidney tissue remains disputed. Here, the most commonly
proposed hypotheses are detailed in the context of the molecule’s
structure, the symptoms seen following ingestion, and its characteristic
prolonged latency period. Chromatographic analysis of orellanine and
its related substances remains challenging, while biological evaluation
of the compound is complicated by uncertainty regarding the role of
active metabolites. This has limited efforts to structurally refine
the molecule; despite numerous established methods for its synthesis,
there is minimal published material on how orellanine’s structure
might be optimized for therapeutic use. Despite these obstacles, orellanine
has generated promising data in preclinical studies of metastatic
clear cell renal cell carcinoma, leading to the early 2022 announcement
of phase I/II trials in humans.