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Strengthening our approach, the majority of active compounds found in the screen have known antineoplastic indications or are being investigated for oncology purposes. Among the latter, we find compounds used as antiparasitics, antiprotozoals, antiinflammatories as well as agents for the treatment of heart diseases. We further validated the activity of 53 compounds in 3D tumor models of pediatric cancers using a multiparametric qHTS assay. Specifically, we found that antiparasitics reduce TC32 cell viability via induction of apoptosis.

Antiparasitic such as mebendazole and difluoromethylornithine DFMO are currently in clinical trials for pediatric brain tumors and neuroblastomas. Our findings further indicate that antiparasitics could have therapeutic potential for a broad range of tumor types. Our study has several limitations. Most importantly, although our extensive quantitative profiling of nearly four thousand drugs generated over half a million data points, we studied a relatively small number of cell lines of several tumor types, which particularly limits the identification of tumor-specific agents. In addition, paired control cell lines for each tumor type might better reflect broad vs.

For the primary and secondary screens, the assay readout is only a proxy for cell viability and orthogonal readouts might strengthen these findings, as seen in our 3D spheroid validation assay.

A high-throughput whole cell screen to identify inhibitors of Mycobacterium tuberculosis

Finally, efficacy in other biologically relevant models of childhood cancer, such as xenograft studies, should be tested to corroborate our findings. We conclude that phenotypic qHTS is a valuable approach to identify new compounds and classes of drugs which merit additional attention for the treatment of pediatric solid tumors.

In concert with informatics approaches, qHTS is useful for prioritizing drugs that already have safety profiles in children further facilitating drug development for pediatric solid tumors. The dataset generated here, along with the CPC, is fully available to the scientific community, and we hope that it will serve as valuable resource to accelerate drug repurposing.

Bernard Weissman and Ian Davis. All cell lines were authenticated by short-tandem repeat STR, 10 loci profiling and routinely tested for mycoplasma contamination using MycoAlert mycoplasma detection kit Lonza. The MIPE Mechanism Interrogation Plate collection contains 1, oncology-focused agents, many of which also have been approved for human use or are under clinical trials [ 18 — 20 ]. Twenty three nL of compounds and controls neutral control DMSO or positive control bortezomib at final concentration of 2.

For primary screens, the MIPE collection was tested at point dilutions final concentration range from 0. Compounds tested in follow-up screens were assayed at point dilutions final concentration range from 0.

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Ninety two nL of compounds and controls neutral control DMSO or positive control bortezomib at final concentrations of 0. Dyes were incubated for 1 hour before imaging using the Celigo Image Cytometer. The data were exported to Excel, and the average fluorescent intensities were used to calculate the ratio of PI over Hoechst, which was used to quantify viability. Percent activity based on neutral and positive control bortezomib was derived and fitted as described in the qHTS data analysis and statistics section below. Spheroids were first identified using bright-field segmentation, and the average fluorescent intensity of the green channel was used to quantify caspase activation as percent activity based on neutral and positive controls see qHTS data analysis and statistics below.

Data from each assay were normalized plate-wise to corresponding intra-plate controls as described previously [ 46 ]. Dose-response curves were classified as described previously [ 22 ]. Data sets were generated for each cell line against each of the drugs which included an activity score based on potency IC 50 , maximum responses, curve classes, fit log IC 50 , and fit Hill slopes. Compounds exhibiting high-quality CRCs class -1 and -2 , and CellTiter-Glo signals six standard deviations below the population of neutral control wells, were considered active.

In the case of spheroid assays, each compound was tested in triplicate. Compounds were considered active when 2 or 3 replicates passed the above cutoffs.

In the heatmap, darker color indicates compounds that are more potent and efficacious, i. In potency-based heatmaps, inactive compounds that have no IC 50 values determined were showed up as grey. We thank Carleen Klumpp-Thomas for assistance with assay automation, the compound management group Paul Shinn, Danielle Bougie, Crystal McKnight, Misha Itkin, and Zina Itkin for sourcing, quality control, formatting, and plating all compounds and Steven Titus for assistance with image acquisition.

This work was supported by the intramural research program of the National Center for Advancing Translational Sciences. Nat Rev Drug Discov. Repurposing approved and abandoned drugs for the treatment and prevention of cancer through public-private partnership. Cancer Res. Blatt J, Corey SJ. Drug repurposing in pediatrics and pediatric hematology oncology.

Drug Discov Today.

Strittmatter SM. Nat Med. Antitumor activity of nifurtimox observed in a patient with neuroblastoma. J Pediatr Hematol Oncol. Propranolol for severe hemangiomas of infancy. N Engl J Med. The emergence of genome-based drug repositioning. Sci Transl Med. Identify drug repurposing candidates by mining the protein data bank.

Brief Bioinform. Swamidass SJ. Mining small-molecule screens to repurpose drugs.

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Literature mining, ontologies and information visualization for drug repurposing. Unveiling the role of network and systems biology in drug discovery. Trends Pharmacol Sci. Yang L, Agarwal P. Systematic drug repositioning based on clinical side-effects. PLoS One. Reaume AG. Drug repurposing through nonhypothesis driven phenotypic screening. Drug Discov Today Ther Strateg. Revisiting old drugs as novel agents for retinoblastoma: in vitro and in vivo antitumor activity of cardenolides.

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Invest Ophthalmol Vis Sci. Ophthalmic Res. In silico and in vitro drug screening identifies new therapeutic approaches for Ewing sarcoma. High-throughput combinatorial screening identifies drugs that cooperate with ibrutinib to kill activated B-cell-like diffuse large B-cell lymphoma cells. High-throughput matrix screening identifies synergistic and antagonistic antimalarial drug combinations.

Sci Rep. The NCGC pharmaceutical collection: a comprehensive resource of clinically approved drugs enabling repurposing and chemical genomics. Quantitative high-throughput screening: a titration-based approach that efficiently identifies biological activities in large chemical libraries. The anthelmintic drug mebendazole induces mitotic arrest and apoptosis by depolymerizing tubulin in non-small cell lung cancer cells.

Mol Cancer Ther.

High Throughput Screening for Novel AntiInflammatories by Kahn & Michael

Drug repurposing and human parasitic protozoan diseases. Mutual action of anticancer and antiparasitic drugs: are there any shared targets?

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  • Future Oncol. Cell Reports. Anti-tumor activity of non-steroidal anti-inflammatory drugs: cyclooxygenase-independent targets. Cancer Lett. Nat Biotechnol. ACS Chem Biol. Digitoxin and its analogs as novel cancer therapeutics. Exp Hematol Oncol. Digitoxin and a synthetic monosaccharide analog inhibit cell viability in lung cancer cells.

    Toxicol Appl Pharmacol. Digitoxin as an anticancer agent with selectivity for cancer cells: possible mechanisms involved. Expert Opin Ther Targets.