CYBREXA: PH-BASED TUMOR TARGETING
By Chris Lieu, Staff Writer
Cybrexa Therapeutics Inc. is developing a targeting technology that taps the pH of the tumor microenvironment to enhance the delivery specificity and decrease the toxicity of small molecule cancer therapies, starting with PARP inhibitors.
Cybrexa uses its alphalex technology to conjugate a cancer agent to a pH-sensitive peptide via an undisclosed linker. The peptide forms a transmembrane α-helix only at a low pH, which occurs in the tumor microenvironment but not normal tissues, and translocates into cells along with its cargo via a non-endocytotic route. Cytoplasmic glutathione cleaves the linker, releasing the free cancer agent inside the cancer cell.
Cybrexa has applied the alphalex technology to PARP inhibitors first because in DNA damage response (DDR)-proficient cancers, PARP inhibitors are most effective in combination with chemotherapy, but the combination leads to toxicities including myelosuppression, nephrotoxicity and hepatotoxicity, said President and CEO Per Hellsund.
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