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15-deoxy-Δ12,14-prostamide J2 (15d-PMJ2) is an investigational small-molecule research compound and an endocannabinoid metabolite. It is produced through the metabolism of arachidonoyl ethanolamide (AEA) by cyclooxygenase-2 (COX-2). 15d-PMJ2 selectively induces apoptosis in various cancer cells, including melanoma, non-melanoma skin cancer (NMSC), and colon cancer, while sparing non-tumorigenic cells. Its mechanism of action involves the induction of endoplasmic reticulum (ER) stress, specifically activating the PERK and CHOP10 pathways, and triggering calcium mobilization from the ER to the mitochondria via the inositol 1,4,5-trisphosphate receptor (IP3R). This calcium flux leads to the opening of the mitochondrial permeability transition pore and subsequent cell death. The compound's cytotoxic activity is dependent on an electrophilic double bond within its cyclopentenone ring. 15d-PMJ2 has demonstrated efficacy in reducing tumor growth in murine melanoma models and is primarily being investigated by academic researchers at East Carolina University.
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