Researchers from the University of Michigan Rogel Cancer Center have worked on creating a therapeutic-based compound that can block the activity of cancer-linked enzymes. The particular family of enzymes examined in the study is known as the nuclear receptor-binding SET domain (NSD). The enzymes are part of a family of histone methyltransferases that have long been studied as an attractive drug target. However, the efforts to attack the activity of these enzymes have been challenging because of the shape of the binding sites where drug-like molecules are supposed to attach.
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To develop the first-in-class inhibitors, Tomasz Cierpicki, Ph.D., and Jolanta Grembecka, used multiple approaches including X-ray crystallography and nuclear magnetic resonance. The work has led to the inhibition of a key protein known as NSD1. Specifically, they developed a compound known as ‘BT5’ and was shown promise in leukemic cells.
Findings were published in Nature Chemical Biology.
"Our study, which was years in the making, demonstrates that targeting this key enzyme with small-molecule inhibitors is a feasible approach," says Cierpicki, an associate professor of biophysics and pathology at U-M. "These findings will facilitate the development of the next generation of potent and selective inhibitors of these enzymes, which are overexpressed, mutated or undergo translocations in several types of cancer."
Source: Science Daily