Juan Pablo Maianti, Ph.D., a member of the National Cancer Institute-designated Montefiore Einstein Comprehensive Cancer Center and assistant professor of biochemistry at Albert Einstein College of Medicine, was awarded a 2024 Pershing Square Sohn Prize for Young Investigators in Cancer Research. Dr. Maianti is one of only five New York City area-based scientists to receive the award this year, which provides $750,000 over three years for innovative basic science cancer research.

The Pershing Square Sohn award specifically supports early-stage “high-risk, high-reward proposals characterized by radically novel scientific approaches that would otherwise not be funded,” according to the group’s website.

Dr. Maianti is working to advance the use of a new class of anti-cancer drugs, compounds that irreversibly adhere to enzymes and other proteins involved in causing cancer. These irreversible small molecules could provide a systematic solution to a major problem in cancer therapy: the fact that so many important enzymes and other oncoproteins are “undruggable” due to molecular structures or other attributes that prevent researchers from targeting them using conventional compounds.

Unlike conventional inhibitors, “irreversible” compounds aren’t limited to targeting only those enzymes offering easy access to their cofactors and catalytic sites. “Using irreversible molecules, we can break that standard paradigm and tackle biomedical targets that are presently impervious to conventional drug discovery approaches,” said Dr. Maianti.

“For decades, finding new treatments for cancer using irreversible drugs has been hindered by the lack of large collections, or libraries, of structurally diverse small molecules that could be screened to identify those that have the perfect reactivity to selectively and irreversibly inhibit cancer-associated proteins,” said Dr. Maianti. To overcome this hurdle, he and his colleagues are establishing a platform to screen millions of DNA-barcoded small molecules fitted with specialized ‘warheads’ to identify the rare compounds that latch onto an oncoprotein.

We believe that irreversible compounds can become a major drug-discovery growth area that will vastly expand the number of actionable targets in anti-cancer therapy.

Juan Pablo Maianti, Ph.D.

“We can now push the boundaries of drug discovery to hit fundamentally more challenging binding sites on proteins,” he said. “This is a vital step for treating cancers that have so far remained untreatable.”

Dr. Maianti added: “Our group is thankful for the opportunity to focus on these most challenging cancer targets that current drug-discovery pipelines aren’t addressing. We believe that irreversible compounds can become a major drug-discovery growth area that will vastly expand the number of actionable targets in anti-cancer therapy.”

Dr. Maianti is the fourth Einstein faculty member to win the Pershing Square Sohn prize; former award winners are Britta Will, Ph.D., Evripidis Gavathiotis, Ph.D., and Maria Soledad Sosa, Ph.D..