Z53 Therapeutics is developing novel compounds that target tumors with p53 mutations.
The p53 protein is known as the "guardian of the human genome" for its central role in suppressing tumor formation. The gene encoding p53 is the most commonly mutated gene in human cancer with a large number of mutations resulting in a defect in the protein's structure due to an impairment in the ability of the protein to bind zinc (aptly called zinc-deficient mutant p53).
Dr. Carpizo and colleagues discovered that small molecules could restore the normal structure and function to zinc-deficient mutant p53. These compounds also increase the formation of reactive oxygen species, which serve to transactivate the newly functional p53 protein. Referred to as zinc metallochaperones, such compounds show great promise as anti-cancer drugs. Z53 Therapeutics aims to utilize this technology to develop a novel class of therapeutics to target tumors containing p53 mutations that show impaired binding of zinc.
Z53 Therapeutics' technology not only addresses a highly unmet clinical need, it also presents a significant commercial opportunity. Each year, 14 million people are diagnosed with cancer worldwide, and half of these diagnoses involve a cancer expressing mutant p53. Cancers with p53 mutations tend to be more resistant to chemotherapy, and, as of this time, there are no approved drugs on the market that specifically target tumors with p53 mutations. Preclinical study results suggest that Z53 Therapeutics' technology may meaningfully advance the standard of care for some cancers.
Our technology is based on discoveries from Rutgers Cancer Institute of New Jersey.
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2. Yu X, Blanden AR, Narayanan S, Jayakumar L, Lubin D, Augeri D, Kimball SD, Loh SN, and Carpizo DR. Small Molecule Restoration of Wildtype Structure and Function of Mutant p53 Using a Novel Zinc-Metallochaperone Based Mechanism. Oncotarget 2014 5(19): 8879-92.
3. Blanden AR, Yu X, Wolfe AJ, Gilleran JA, Augeri D, O’Dell RS, Olson EC, Kimball SD, Emge TJ, Movileanu L, Carpizo DR, and Loh SN. Synthetic Metallochaperone ZMC1 Conformation by Transporting Zinc into Cells as an Ionophore. Mol Pharma 87:825-831.