Spiroarborin, an ent-Clerodane Homodimer from Callicarpa arboreaas 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 1was proposed, and a biomimetic synthesis of its derivative was accomplished. Compound 1showed a potent inhibitory effect by directly binding to the YEATS domain of the 11-19 leukemia (ENL) protein with an IC50value of 7.3 μM. This gave a KDvalue of 5.0 μM, as recorded by a surface plasmon resonance binding assay.