at-13387 and Pancreatic-Neoplasms

Pancreatic ductal adenocarcinoma is one of the deadliest cancers for which few curative therapies are available to date. Heat shock protein 90 (Hsp90) inhibitors have shown activity against numerous cancers in vitro; therefore, we tested whether they could be used to target pancreatic ductal adenocarcinoma.. Inhibitors of Hsp90 ATPase activity were applied on low-passage pancreatic cell line cultures (Panc10.05, Panc215, A6L) in a dose-response manner, and the inhibitor in vitro effect on cell growth was evaluated. Seven of novel Hsp90 inhibitors based on resorcinol fragment and 5 commercially available Hsp90 inhibitors (17-AAG, AT-13387, AUY-922, ganetespib, and rifabutin) as well as control compound triptolide were tested yielding IC50 values in 2- and 3-dimensional assays.. The novel Hsp90 inhibitors exhibited strong effects on all 3 tested pancreatic cell line cultures (Panc10.05, Panc215, A6L) reaching the IC50 of 300 to 600 nM in 2- and 3-dimensional assays.. Novel Hsp90 inhibitors can be developed as antipancreatic cancer agents. Their chemical structures are simpler, and they are likely to exhibit lower side effects than the much more complex inhibitors used as controls.

Topics: Adenosine Triphosphatases; Antineoplastic Agents; Benzamides; Benzoquinones; Carcinoma, Pancreatic Ductal; Cell Culture Techniques, Three Dimensional; Cell Line, Tumor; Cell Proliferation; Dose-Response Relationship, Drug; HSP90 Heat-Shock Proteins; Humans; Isoindoles; Isoxazoles; Lactams, Macrocyclic; Molecular Structure; Pancreatic Neoplasms; Resorcinols; Rifabutin; Triazoles