Spiroarborin, an ent -Clerodane Homodimer from Callicarpa arborea as an Inhibitor of the Eleven-Nineteen Leukemia (ENL) Protein by Targeting the YEATS Domain.

A spiro ent -clerodane homodimer with a rare 6/6/6/6/6-fused pentacyclic scaffold, spiroarborin ( 1 ), together with four new monomeric analogues ( 2 - 5 ), were isolated from Callicarpa arborea . Their structures were elucidated by comprehensive spectroscopic data analysis, quantum-chemical calculations, and X-ray diffraction. A plausible biosynthetic pathway of 1 was proposed, and a biomimetic synthesis of its derivative was accomplished. Compound 1 showed a potent inhibitory effect by directly binding to the YEATS domain of the 11-19 leukemia (ENL) protein with an IC 50 value of 7.3 μM. This gave a K D value of 5.0 μM, as recorded by a surface plasmon resonance binding assay.