WEST LAFAYETTE, Ind. — Researchers in Purdue University's College of Pharmacy have developed and validated a novel series of small-molecule inhibitors that promote antitumor immunity and hold promise as novel anticancer agents.
Zhong-Yin Zhang leads a team that has developed L-32, a quinolone-based inhibitor shown to reduce tumor growth in vivo and improve upon the potency, selectivity and cellular efficacy of previous derivatives of the inhibitor.
L-32 targets a protein tyrosine phosphatase (PTP) called PTPN22, a negative regulator of the immune system. Zhang said mutations in PTPN22 are common risk factors for multiple autoimmune disorders, and genetic deletion of PTPN22 leads to robust antitumor immunity.
"Consequently, targeting PTPN22 with small-molecule inhibitors represents an attractive immunotherapeutic strategy to unleash both innate and adaptive immunity against tumor cells," he said.
Zhang said PTPN22 remains underexplored as a therapeutic target despite its known roles in cancer immunity.
"This is due to the scarcity of high-quality small-molecule inhibitors," he said. "Consequently, we have advanced a novel paradigm to acquire potent and selective PTP inhibitors by targeting both the active site and its nearby unique pockets."
Zhang is a Distinguished Professor of medicinal chemistry in the Borch Department of Medicinal Chemistry and Molecular Pharmacology , a member of the Purdue Institute for Cancer Research , and director of the Purdue Institute for Drug Discovery .
The research has been published in the Journal of Medicinal Chemistry . Zhang disclosed the quinolone-based PTPN22 inhibitors, including L-32, to the Purdue Innovates Office of Technology Commercialization , which applied for a patent from the U.S. Patent and Trademark Office to protect the intellectual property.
