{"id":5024,"date":"2024-06-20T21:21:00","date_gmt":"2024-06-20T21:21:00","guid":{"rendered":"https:\/\/new.www.purdue.edu\/newsroom\/?post_type=purduetoday&p=5024"},"modified":"2024-08-20T11:08:52","modified_gmt":"2024-08-20T15:08:52","slug":"like-a-hand-fitting-into-a-glove-purdue-engineered-compound-designed-to-treat-drug-resistant-acute-myeloid-leukemia","status":"publish","type":"post","link":"https:\/\/www.purdue.edu\/newsroom\/2024\/Q2\/like-a-hand-fitting-into-a-glove-purdue-engineered-compound-designed-to-treat-drug-resistant-acute-myeloid-leukemia","title":{"rendered":"\u2018Like a hand fitting into a glove\u2019: Purdue-engineered compound designed to treat drug-resistant acute myeloid leukemia"},"content":{"rendered":"

WEST LAFAYETTE, Ind. —<\/p> \n

Researchers at Purdue University\u2019s\u00a0College of Science<\/a>\u00a0have developed a patent-pending compound called HSN748 to treat drug-resistant acute myeloid leukemia (AML). AML is a cancer that begins in bone marrow and sometimes metastasizes to the central nervous system, liver, lymph nodes, spleen and testicles.<\/p>\n<\/div>\n\n\n

Herman Sintim<\/a> leads the team that has developed the compound. He is a Distinguished Professor in Chemistry and the Richard B. Wetherill Professor of Chemistry and Drug Discovery in the James Tarpo Jr. and Margaret Tarpo Department of Chemistry<\/a>. He also is on the faculty of the Purdue Institute for Cancer Research<\/a> and the Purdue Institute for Drug Discovery<\/a>.<\/p>\n\n\n

\n
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Herman Sintim (Photo provided)<\/em><\/figcaption><\/figure>\n<\/div>\n\n\n

Sintim\u2019s development team collaborated with a group including Reuben Kapur<\/a> and Baskar Ramdas<\/a> at the Indiana University School of Medicine<\/a> and KinaRx Inc.<\/a> to validate the effectiveness of the compound. Kapur is the director of the Herman B Wells Center for Pediatric Research and co-leader of the Hematopoiesis and Hematologic Malignancies program at the IU Melvin and Bren Simon Comprehensive Cancer Center. Ramdas is an assistant research professor of pediatrics. KinaRx is an early-stage biotechnology company developing novel kinase inhibitors for cancer. It received a $2 million Small Business Innovation Research grant from the National Institutes of Health to fund the research.<\/p>\n\n\n\n

They demonstrated that HSN748 effectively treated mice implanted with patient-derived, drug-resistant AML with 100% survivability after 120 days. Their co-authored paper of research results has been published in the Journal of Clinical Investigation<\/a>.<\/p>\n\n\n\n

Sintim disclosed HSN748 to the Purdue Innovates Office of Technology Commercialization<\/a>, which has applied for a patent to protect the intellectual property. <\/p>\n\n\n\n

AML metrics and traditional treatments<\/strong> <\/h2>\n\n\n\n

The National Cancer Institute estimates<\/a> 20,800 new cases of AML will be diagnosed in 2024, which would represent 1% of new cancer cases in the U.S. It is most often diagnosed in people between the ages of 65 and 74, with a median age of 69. Although uncommon, AML can occur in children. The five-year relative survival rate is 31.9%.<\/p>\n\n\n\n

Sintim said, \u201cOne of the best U.S. Food and Drug Administration-approved drugs right now to treat AML is called gilteritinib (Xospata). But patients have developed genetic mutations in an enzyme called FLT3 that could render gilteritinib ineffective.\u201d<\/p>\n\n\n\n

Ramdas said, \u201cDespite the widespread occurrence and clinical importance of FLT3 mutations in causing AML, treatment options tailored to this genetic anomaly are scarce. Our goal was to identify new and powerful inhibitors targeting the mutations, particularly those resistant to currently approved FDA options.\u201d<\/p>\n\n\n\n

How HSN748 works<\/strong> <\/h2>\n\n\n\n

Sintim and his team have identified inhibitors, or blocking agents, that target FLT3 gene mutations, the most common mutation in AML. Sintim used the three-dimensional atomic structure of FLT3 to address the challenges of drug resistance. <\/p>\n\n\n\n

\u201cThe three-dimensional atomic structure guided the molecular design and synthesis of HSN748 so it fits perfectly into the active site of drug-resistant mutants of FLT3, like a hand fitting into a glove,\u201d Sintim said. \u201cThe enzymatic activity of FLT3 is crucial for AML cancer cell survival, so filling in the active site with HSN748 kills the enzyme\u2019s activity and also kills the cancer cells.\u201d<\/p>\n\n\n\n

Sintim continued, \u201cRemarkably, while all mice that had been implanted with gilteritinib-resistant human patient AML samples and were treated with HSN748 were alive by day 120, none of the animals treated with gilteritinib survived past day 120, demonstrating the superiority of this investigational drug over the FDA-approved drug.\u201d<\/p>\n\n\n

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Figure shows that the investigational drug HSN748, developed by Purdue researchers, outperforms the FDA-approved drug gilteritinib using a mouse model harboring a drug-resistant AML sample. (Image provided by Herman Sintim)<\/em><\/figcaption><\/figure>\n<\/div>\n\n\n

Kapur said, \u201cOur preclinical study results have shown incredible promise, and we\u2019re excited to keep the momentum going so AML patients can have more resilient options.\u201d <\/p>\n\n\n\n

Next development steps<\/strong><\/h2>\n\n\n\n

Sintim is one of the founders of KinaRx, which has licensed HSN748 from the Purdue Innovates Office of Technology Commercialization.<\/p>\n\n\n\n

Sintim said the next stage to develop the compound is clinical trials.<\/p>\n\n\n\n

\u201cWe are at the planning stage and looking to secure investments from different types of investors,\u201d he said.<\/p>\n\n\n\n

Prospective funders and physicians interested in learning about the studies can contact Sintim<\/a>. <\/p>\n\n\n\n

About Purdue Innovates Office of Technology Commercialization<\/strong><\/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 2023, the office reported 150 deals finalized with 203 technologies signed, 400 disclosures received and 218 issued U.S. patents. The office is managed by the Purdue Research Foundation, which received the 2019 Innovation & Economic Prosperity Universities Award for Place from the Association of Public and Land-grant Universities. In 2020, IPWatchdog Institute ranked Purdue third nationally in startup creation and in the top 20 for patents. The Purdue Research Foundation is 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<\/strong><\/h2>\n\n\n\n

Purdue University is a public research institution demonstrating excellence at scale. Ranked among top 10 public universities and with two colleges in the top four in the United States, Purdue discovers and disseminates knowledge with a quality and at a scale second to none. More than 105,000 students study at Purdue across modalities and locations, including nearly 50,000 in person on the West Lafayette campus. Committed to affordability and accessibility, Purdue\u2019s main campus has frozen tuition 13 years in a row. See how Purdue never stops in the persistent pursuit of the next giant leap \u2014 including its first comprehensive urban campus in Indianapolis, the Mitchell E. Daniels, Jr. School of Business, Purdue Computes and the One Health initiative \u2014 at https:\/\/www.purdue.edu\/president\/strategic-initiatives<\/a>.<\/p>\n","protected":false},"excerpt":{"rendered":"

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