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The protein made by the ASH1L gene plays a key role in the development of acute leukemia, along with other diseases. The ASH1L protein, however, has been challenging to target therapeutically.
Now a team of researchers led by Jolanta Grembecka, Ph.D., and Tomasz Cierpicki, Ph.D., from the University of Michigan has developed first-in-class small molecules to inhibit ASH1L’s SET domain—preventing critical molecular interactions in the development and progression of leukemia.
The team’s findings, vitamins and lexapro interaction which used fragment-based screening, followed by medicinal chemistry and a structure-based design, appear in Nature Communications.
In mouse models of mixed lineage leukemia, the lead compound, known as AS-99, successfully reduced leukemia progression.
“This work points to a new, exiting avenue to develop new therapeutic agents against acute leukemia, as well as providing a new approach to further study the biological functions of ASH1L and its role in the development of the disease,” says Grembecka, associate professor of pathology at Michigan Medicine and co-director of the developmental therapeutics program at the U-M Rogel Cancer Center.
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