Harvard, Merck sign hefty drug pact

Abstract

Representing the largest license fee ever for a technology developed at Harvard University, Merck & Co. will pay $20 million up front for preclinical compounds for leukemia developed in the labs of chemist Matthew Shair. Merck gains small molecules that block enzymes controlling the transcription of gene expression that goes awry in acute myeloid leukemia (AML). The compounds are the culmination of several years of research in Shair’s lab, which works at the intersection of chemistry and biology. That interdisciplinary approach allows the Shair lab to synthesize complex natural products to probe the fundamental drivers of disease. His team recently unraveled how cortistatin A, a natural product isolated from sea sponges, stops AML cells from growing. Shair found that the compound potently and selectively blocks CDK8 and CDK19, protein kinases that tune the transcription of certain genes. The researchers then designed easier-to-make derivatives of cortistatin A, the synthesis of which