PTGES3-PROTAC

PTGES3-PROTAC is an **experimental peptide-based proteolysis-targeting chimera (PROTAC) drug** designed to selectively degrade **prostaglandin E synthase 3 (PTGES3, also known as p23)**, a protein implicated in the malignant progression of several cancers, most notably hepatocellular carcinoma (HCC)[1][2]. The drug consists of a **liposomal complex containing a PTGES3-binding peptide (FIP-2), a cell-penetrating TAT peptide, and the E3 ubiquitin ligase ligand pomalidomide**, linked through DSPE-PEG2000 derivatives. PTGES3-PROTAC induces selective, efficient, and sustained **ubiquitin–proteasome-dependent degradation of PTGES3 in cancer cells**, suppressing cell proliferation, migration, and tumor growth both in vitro and in vivo. In preclinical animal models, PTGES3-PROTAC showed good tumor localization and minimal toxicity to normal organs[1]. The approach allows for targeted modulation of PTGES3, an “undruggable” protein with both enzymatic (prostanoid synthesis) and chaperone (Hsp90 co-chaperone) activities[1][2][4].