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ID: ALA5154724

Journal: Bioorg Med Chem

Title: Cathepsin D inhibitors based on tasiamide B derivatives with cell membrane permeability.

Authors: Li Z, Li H, Jiang F, Wang Z, Zhang W.

Abstract: Cathepsin D (Cath D) has been evidenced as a potential target for cancer therapy. Our previous studies revealed that TB-9, a tasiamide B derivative, exhibited highly potent inhibition against Cath D with satisfactory selectivity over Cath E and BACE1. But this compound was inactive on cell level possibly due to poor membrane permeability. Herein, we report the design, synthesis, and evaluation of two novel Cath D inhibitors (2 and 3) which combining tasiamide B scaffold with a cell penetrating peptide (CPP) specifically targeting the endolysosomal compartment. The results revealed that 2 and 3 not only retained highly potent inhibition against Cath D, but also were active against MDA-MB-231 cell lines.

CiteXplore: 35121401

DOI: 10.1016/j.bmc.2022.116646