tanespimycin and Nasopharyngeal-Neoplasms

Hsp90 is a new promising target for cancer treatment. Many inhibitors have been discovered as therapeutic agents, and some have passed Phase I and II. However, no one is approved by FDA yet. Novel and druggable Hsp90 inhibitors are still demanding. Here, we report a new way to discover high potent Hsp90 inhibitors as antinasopharyngeal carcinoma agents through assembling fragments. With chemotyping analysis, we extract seven chemotypes from 3482 known Hsp90 inhibitors, screen 500 fragments that are compatible with the chemotypes, and confirm 15 anti-Hsp90 fragments. Click chemistry is employed to construct 172 molecules and synthesize 21 compounds among them. The best inhibitor 3d was further optimized and resulted in more potent 4f (IC

Topics: Animals; Antineoplastic Agents; Cell Line, Tumor; Databases, Chemical; HSP90 Heat-Shock Proteins; Humans; Male; Mice, Nude; Molecular Dynamics Simulation; Nasopharyngeal Carcinoma; Nasopharyngeal Neoplasms; Protein Binding; Small Molecule Libraries; Triazoles; Xenograft Model Antitumor Assays