{"id":23010,"date":"2026-08-24T08:10:05","date_gmt":"2026-08-24T12:10:05","guid":{"rendered":"https:\/\/www.purdue.edu\/newsroom\/?p=23010"},"modified":"2026-08-24T08:10:14","modified_gmt":"2026-08-24T12:10:14","slug":"purdue-small-molecule-inhibitors-shown-to-promote-robust-antitumor-immunity","status":"publish","type":"post","link":"https:\/\/www.purdue.edu\/newsroom\/2026\/Q3\/purdue-small-molecule-inhibitors-shown-to-promote-robust-antitumor-immunity","title":{"rendered":"Purdue small-molecule inhibitors shown to promote robust antitumor immunity"},"content":{"rendered":"\n

WEST LAFAYETTE, Ind. \u2014 Researchers in Purdue University\u2019s College of Pharmacy<\/a> have developed and validated a novel series of small-molecule inhibitors that promote antitumor immunity and hold promise as novel anticancer agents.<\/p>\n\n\n\n

Zhong-Yin Zhang<\/a> 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.<\/p>\n\n\n\n

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.<\/p>\n\n\n\n

\u201cConsequently, targeting PTPN22 with small-molecule inhibitors represents an attractive immunotherapeutic strategy to unleash both innate and adaptive immunity against tumor cells,\u201d he said.<\/p>\n\n\n\n

Zhang said PTPN22 remains underexplored as a therapeutic target despite its known roles in cancer immunity.<\/p>\n\n\n\n

\u201cThis is due to the scarcity of high-quality small-molecule inhibitors,\u201d he said. \u201cConsequently, we have advanced a novel paradigm to acquire potent and selective PTP inhibitors by targeting both the active site and its nearby unique pockets.\u201d<\/p>\n\n\n\n

Zhang is a Distinguished Professor of medicinal chemistry in the Borch Department of Medicinal Chemistry and Molecular Pharmacology<\/a>, a member of the Purdue Institute for Cancer Research<\/a>, and director of the Purdue Institute for Drug Discovery<\/a>.<\/p>\n\n\n\n

The research has been published in the Journal of Medicinal Chemistry<\/a>. Zhang disclosed the quinolone-based PTPN22 inhibitors, including L-32, to the Purdue Innovates Office of Technology Commercialization<\/a>, which applied for a patent from the U.S. Patent and Trademark Office to protect the intellectual property.<\/p>\n\n\n\n

Industry partners interested in developing or commercializing the inhibitors should contact Joe Kasper, assistant director of business development and licensing \u2014 life sciences, at jrkasper@prf.org<\/a> about track code 68996<\/a>.<\/p>\n\n\n\n

Developing, validating L-32<\/h2>\n\n\n\n

Zhang and his team discovered quinolone-3-carboxylic acid as a PTPN22 inhibitor from an in-house, druglike small molecule collection.<\/p>\n\n\n\n

\u201cUsing a fragment-based focused library approach by tethering properly functionalized small molecule fragments to the quinolone core, we identified compound L-32, which displays improved potency, selectivity and cellular efficacy compared to previous compounds,\u201d he said.<\/p>\n\n\n\n

Zhang said L-32 has several advantages over the other compounds, including a more favorable pharmacokinetic profile and drug properties including oral bioavailability.<\/p>\n\n\n\n

\u201cImportantly, L-32 is superior to early molecules in reducing syngeneic MC38 tumor growth in animal models by promoting robust antitumor immunity, thus offering a promising lead molecule for the development of novel anticancer agents targeting PTPN22,\u201d he said.<\/p>\n\n\n\n

Next steps to develop L-32<\/h2>\n\n\n\n

Zhang said the next steps to further develop the PTPN22-targeting drugs are optimizing L-32 and benchmarking in vivo efficacy.<\/p>\n\n\n\n

\u201cIn particular, we will be expanding the testing for L-32 in more difficult-to-treat cancers including pancreatic and liver cancers, as well as in cancers resistant to current immunotherapies,\u201d he said.<\/p>\n\n\n\n

This research was supported in part by the National Institutes of Health and the Robert C. and Charlotte Anderson Chair Endowment.<\/p>\n\n\n\n

About Purdue Innovates Office of Technology Commercialization<\/h2>\n\n\n\n

The Purdue Innovates Office of Technology Commercialization<\/a> operates one of the most comprehensive technology transfer programs among leading research universities in the U.S. Services provided by this office support the economic development initiatives of Purdue University and benefit the university\u2019s academic activities through commercializing, licensing and protecting Purdue intellectual property. In fiscal year 2025, the office reported 161 deals executed with 269 technologies licensed, 479 invention disclosures received, and 267 U.S. and international patents received. The office is managed by the Purdue Research Foundation, a private, nonprofit foundation created to advance the mission of Purdue University. Contact otcip@prf.org<\/a> for more information. <\/p>\n\n\n\n

About Purdue University<\/h2>\n\n\n\n

Purdue University is a research institution ranked among the top 10 public universities in the United States. More than 106,000 students study at Purdue across multiple campuses, including more than 57,000 at our main campus locations in West Lafayette and Indianapolis. As a land-grant university committed to affordability and accessibility, Purdue\u2019s main campus has frozen tuition 14 years in a row, enabling more students than ever to graduate debt-free.<\/p>\n\n\n

\n
\n
\n

\n Media contact:<\/strong> Steve Martin, sgmartin@prf.org<\/a> <\/p>\n <\/div>\n <\/div>\n<\/div>\n","protected":false},"excerpt":{"rendered":"

WEST LAFAYETTE, Ind. \u2014 Researchers in Purdue University\u2019s 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<\/p>\n","protected":false},"author":25,"featured_media":23008,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_acf_changed":false,"footnotes":""},"categories":[316],"tags":[],"department":[],"source":[35],"purdue_today_topic":[],"coauthors":[44],"class_list":["post-23010","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-prf","source-purdue-research-foundation"],"acf":[],"_links":{"self":[{"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/posts\/23010","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/users\/25"}],"replies":[{"embeddable":true,"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/comments?post=23010"}],"version-history":[{"count":1,"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/posts\/23010\/revisions"}],"predecessor-version":[{"id":23011,"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/posts\/23010\/revisions\/23011"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/media\/23008"}],"wp:attachment":[{"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/media?parent=23010"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/categories?post=23010"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/tags?post=23010"},{"taxonomy":"department","embeddable":true,"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/department?post=23010"},{"taxonomy":"source","embeddable":true,"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/source?post=23010"},{"taxonomy":"purdue_today_topic","embeddable":true,"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/purdue_today_topic?post=23010"},{"taxonomy":"author","embeddable":true,"href":"https:\/\/www.purdue.edu\/newsroom\/wp-json\/wp\/v2\/coauthors?post=23010"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}