Prostaglandin reductase 1 (PTGR1) (PTGR1)

Prostaglandin reductase 1 (PTGR1) is a cytosolic enzyme belonging to the medium-chain dehydrogenase/reductase family, primarily known for its role in the metabolic inactivation of prostaglandins and leukotrienes (UniProt P41273). In the context of oncology, PTGR1 has gained significant attention as the essential activating enzyme for LP-184, a next-generation acylfulvene prodrug (Lantern Pharma). PTGR1 catalyzes the reduction of LP-184 into a highly reactive alkylating species that creates bulky DNA adducts, leading to cell death particularly in tumors with DNA damage repair deficiencies (PubMed 34155108). Because PTGR1 is frequently overexpressed in various solid tumors, including pancreatic, prostate, and lung cancers, it serves as both a therapeutic trigger and a predictive biomarker for drug sensitivity (PubMed 35453958). This targeted activation mechanism aims to enhance the therapeutic index by concentrating the cytotoxic effect within the tumor microenvironment while sparing tissues with low PTGR1 expression.

Other names

Leukotriene B4 12-hydroxydehydrogenaseLTB4DHPGR1ZADH115-oxoprostaglandin 13-reductase

PTGR1 acts as a bioactivating enzyme that reduces the prodrug LP-184 into its active, cytotoxic form, which then induces lethal DNA damage through the formation of bulky DNA adducts (PubMed 34155108).