Definition

A conjugate composed of a pH low insertion peptide (pHLIP) linked to the camptothecin analog exatecan, with potential antineoplastic activity. Upon administration of pHLIP-exatecan conjugate CBX-12, the pHLIP moiety specifically targets and gets inserted into the cellular membrane of tumor cells in environments with low extracellular pH. Then the exatecan moiety is released intracellularly via glutathione reduction of the linker. Exatecan inhibits DNA topoisomerase I activity, thereby inhibiting DNA replication and resulting in cell cycle arrest and tumor cell apoptosis. Tumor cell environments are more acidic than normal, healthy tissue environments. The pHLIP forms an alpha helix and becomes inserted across the cell membrane specifically at the low extracellular pH found within tumors.