Ac-Phe-Lys-PABC-DOX

Ac-Phe-Lys-PABC-DOX (PDOX) is a cathepsin B-cleavable prodrug of doxorubicin designed for targeted cancer therapy. The prodrug consists of doxorubicin conjugated to a cathepsin B-specific dipeptide (Phe-Lys) via a self-immolative spacer, para-aminobenzyloxycarbonyl (PABC). This design allows PDOX to remain stable and inactive in blood circulation and normal tissues. When PDOX reaches cathepsin B-enriched tumor sites, the dipeptide is cleaved by cathepsin B, exposing the PABC spacer which is then spontaneously hydrolyzed to release free doxorubicin directly into cancer cells. This targeted delivery mechanism aims to enhance antitumor efficacy while reducing systemic toxicities compared to free doxorubicin, particularly cardiotoxicity. The molecular weight is 1045.5 g/mol with 52.0% doxorubicin content. Preclinical studies have demonstrated superior anticancer effects with reduced toxicity to liver, kidney, and heart in animal models of gastric cancer, liver cancer, and breast cancer. The mechanism involves inducing apoptosis via the mitochondria-centered intrinsic pathway, with increased ROS generation, cytochrome c release, cell cycle arrest at G2/S phase, and reduced ERK1/2 phosphorylation.

Other names

Ac-Phe-Lys-PABC-doxorubicinAc-Phe-Lys-PABC-ADM