New breakthrough in cancer-targeted drug screening

Researchers at the National Center for Advanced Translational Sciences (NCATS) at the National Institutes of Health have developed a system that accelerates the discovery of compounds that inhibit a variety of cancer-related enzymes. The study was published recently in the journal Biological Chemistry.
NSD2 is active in cancers such as acute lymphoblastic leukemia and certain types of multiple myeloma, inhibiting NSD2 activity seems to be a promising strategy for treating these conditions. So far, however, researchers have not been able to find any chemicals that reliably block NSD2.
finding chemical inhibitors for NSD2 is partly because the enzyme is difficult to operate in the lab. NSD2 modifies histoproteins, the proteins around DNA. For technical reasons, scientists often use fragments of enzymes and histogenes to study this activity. However, NSD2 applies only to the entire nuclear gadget.
"enzymes like NSD2 are very picky because they prefer to work only on the entire nucleosome, " the authors said. In collaboration with biotech company Action Biology, the authors developed a laboratory testing process involving the entire nucleosome that can be used to observe whether NSD2 can modify histogens in the presence of various compounds. The compounds tested by the team came from NCATS' vast pool of bioactive chemicals.
but finding compounds that block NSD2 activity is just the beginning. To confirm that the chemicals identified in the initial large-scale screening were indeed reliable and repeatable, the NCATS team needed to use a variety of bio-chemical methods to confirm the activity of each compound.
"We screened 16,000 molecules, and we got 174 positive feedback, but that doesn't mean they all work," the authors said.
several molecules have now been proven in several screenings, and Hall's team hopes to continue to look for reliable NSD2 inhibitors that can be used as both research tools and promising drugs. (Bio Valley)