Four clinically utilized drugs were identified and validated for treatment of adrenocortical cancer using quantitative high-throughput screening.

摘要: Drug repurposing for cancer treatment is an emerging approach to discover clinically approved drugs that demonstrate antineoplastic effect. The effective therapeutics patients with advanced adrenocortical carcinoma(ACC) are greatly needed. objective of this study was identify and validate effect in ACC cells using a novel quantitative high-throughput drug screening (qHTS) technique. A proliferation assay 2,816 performed the NCI-H295R cell line. We validated antiproliferative candidate compounds cells. Further validation 3-dimensional multicellular aggregates (MCA) SW-13 lines. identified 79 active against cells; 21 had efficacy ≥60% IC50 <1 μM. top categories enriched were cardiotonic, antiseptic, antineoplastic. selected Bortezomib, ouabain, Methotrexate, pyrimethamine validation. All monolayer culture at clinical achievable serum level. Bortezomib ouabain inhibited growth MCA both lines low concentration (10 fold below IC50). Methotrexate caused disintegration concentrations well maximum level 100 Pyrimethamine inhibition 10 concentration. qHTS previously efficient method anticancer rare such as ACC. have pyrimethamine, which could be translated into trials locally and/or metastatic