LAUSR

Doublecortin-like kinase 1 (DCLK1) is a serine/threonine kinase that is overexpressed in gastrointestinal cancers, including esophageal, gastric, colorectal and pancreatic cancers. DCLK1 is also used as a marker of tuft cells, which regulate Type II immunity in the gut. However, the substrates and functions of DCLK1 are understudied. We recently described the first selective DCLK1/ 2 inhibitor, DCLK1-IN-1, developed to aid the functional characterization of this important kinase. Here we describe the synthesis and structure activity relationships of 5,11-dihydro-6H-benzo[e]pyrimido[5,4-b][1,4]diazepin-6-one DCLK1 inhibitors, resulting in the identification of DCLK1-IN-1.