Xylarimides A and B, Unusual 21 Membered Cyclic Depsipeptides Featuring a 3-Furan-2-Hydroxypropionic Acid Unit, Target ATG7 to Induce Lethal Autophagy in Renal Cancer Cells

Xylarimides A and B, two novel 21-membered cyclic depsipeptides, were isolated from the fungus Xylaria striata. Both compounds feature a previously undescribed 3-furan-2-hydroxypropionic acid moiety. Xylarimide A potently inhibits the proliferation of the renal cancer cell lines and the growth of 786-O xenografts in a mouse model. Mechanistically, xylarimide A activates autophagic flux while suppressing AKT-mTOR signaling by directly targeting the core protein ATG7, inducing lethal autophagy.