SynToxProfiler: An interactive analysis of drug combination synergy, toxicity and efficacy. by Aleksandr Ianevski, Sanna Timonen, Alexander Kononov, Tero Aittokallio, Anil K Giri

“…When applied to 20 anti-cancer drug combinations tested both in healthy control and T-cell prolymphocytic leukemia (T-PLL) patient cells, as well as to 77 anti-viral drug pairs tested in Huh7 liver cell line with and without Ebola virus infection, SynToxProfiler prioritized as top hits those synergistic drug pairs that showed higher selective efficacy (difference between efficacy and toxicity), which offers an improved likelihood for clinical success.…”
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Novel inhibitors of a Grb2 SH3C domain interaction identified by a virtual screen by Simister, P, Luccarelli, J, Thompson, S, Appella, D, Feller, S, Hamilton, A

“…A virtual screen was conducted for putative binders of the Grb2 SH3C domain. Of the top hits, 34 were validated experimentally by surface plasmon resonance spectroscopy and isothermal titration calorimetry. …”

Computer-Aided Drug Design Of Potential Neuraminidase Inhibitors From Plant Extracts by Muchtaridi, Muchtaridi

“…Virtual screening results showed that xanthone derivatives from G. mangostana (mangosteen) were the top hits, thus provide rationale to select this plant for further isolation. …”
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Selenosugars targeting the infective stage of Trypanosoma brucei with high selectivity by Estefanía Dibello, Natalia Oddone, Jaime Franco, Tünde-Zita Illyés, Andrea Medeiros, Attila Kiss, Fanni Hőgye, Katalin E. Kövér, László Szilágyi, Marcelo A. Comini

“…Earlier evidences showed that diglycosyl diselenides are active against the infective stage of African trypanosomes (top hits IC50 0.5 and 1.5 μM) but poorly selective (selectivity index <10). …”
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Cohesin mutations are synthetic lethal with stimulation of WNT signaling by Chue Vin Chin, Jisha Antony, Sarada Ketharnathan, Anastasia Labudina, Gregory Gimenez, Kate M Parsons, Jinshu He, Amee J George, Maria Michela Pallotta, Antonio Musio, Antony Braithwaite, Parry Guilford, Ross D Hannan, Julia A Horsfield

“…Unexpectedly, one of the top ‘hits’ was a GSK3 inhibitor, an agonist of Wnt signaling. …”
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Mining small RNA structure elements in untranslated regions of human and mouse mRNAs using structure-based alignment by Wen Dongrong, Liu Jianghui, Khaladkar Mugdha, Wang Jason TL, Tian Bin

“…This approach resulted in 90 distinct RNA structure groups containing 748 structures, with HSL3 and IRE among the top hits based on conservation of structure.</p> <p>Conclusion</p> <p>Our result indicates that there may exist many conserved stem-loop structures in mammalian UTRs that are involved in coordinate post-transcriptional regulation of biological pathways.…”
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Comparative analysis of radiosensitizers for K-RAS mutant rectal cancers. by Laura B Kleiman, Angela M Krebs, Stephen Y Kim, Theodore S Hong, Kevin M Haigis

“…Using this screening platform and K-RAS mutant rectal cancer cell lines, we tested SMIs targeting diverse signaling pathways for radiosensitizing activity and then evaluated our top hits in follow-up experiments. The two most potent radiosensitizers were the Chk1/2 inhibitor AZD7762 and the PI3K/mTOR inhibitor BEZ235. …”
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Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer by Hosseini, A, Lindholm, HT, Chen, R, Mehdipour, P, Marhon, SA, Ishak, CA, Moore, PC, Classon, M, Di Gioacchino, A, Greenbaum, B, De Carvalho, DD

“…Here, we systematically identify mechanisms of viral mimicry adaptation associated with cancer cell dependencies. Among the top hits is the RNA decay protein XRN1 as an essential gene for the survival of a subset of cancer cell lines. …”

A CRISPR screen identifies redox vulnerabilities for KEAP1/NRF2 mutant non-small cell lung cancer by Chang Jiang, Nathan P. Ward, Nicolas Prieto-Farigua, Yun Pyo Kang, Anish Thalakola, Mingxiang Teng, Gina M. DeNicola

“…While our screen identified expected hits in the pentose phosphate pathway, the thioredoxin-dependent antioxidant system, and glutathione reductase, we also identified the mitochondrial superoxide dismutase 2 (SOD2) as one of the top hits. Surprisingly, β-Lapachone did not generate mitochondrial O2•– but rather SOD2 loss enhanced the efficacy of β-Lapachone due to loss of iron-sulfur protein function, loss of mitochondrial ATP maintenance and deficient NADPH production. …”
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Retroelement decay by the exonuclease XRN1 is a viral mimicry dependency in cancer by Amir Hosseini, Håvard T. Lindholm, Raymond Chen, Parinaz Mehdipour, Sajid A. Marhon, Charles A. Ishak, Paul C. Moore, Marie Classon, Andrea Di Gioacchino, Benjamin Greenbaum, Daniel D. De Carvalho

“…Here, we systematically identify mechanisms of viral mimicry adaptation associated with cancer cell dependencies. Among the top hits is the RNA decay protein XRN1 as an essential gene for the survival of a subset of cancer cell lines. …”
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ICE1 promotes the link between splicing and nonsense-mediated mRNA decay by Thomas D Baird, Ken Chih-Chien Cheng, Yu-Chi Chen, Eugen Buehler, Scott E Martin, James Inglese, J Robert Hogg

“…Canonical members of the NMD pathway were highly enriched as top hits in the siRNA screen, along with numerous candidate NMD factors, including the conserved ICE1/KIAA0947 protein. …”
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High-Throughput Screening for Inhibitors of the SARS-CoV-2 Protease Using a FRET-Biosensor by Alistair S. Brown, David F. Ackerley, Mark J. Calcott

“…The screening identified 65 inhibitors, with the 20 most active exhibiting sub-micromolar inhibition of 3CL^pro in follow-up EC₅₀ assays. The top hits included several compounds not previously identified as 3CL^pro inhibitors, in particular five members of a family of aporphine alkaloids that offer promise as new antiviral drug leads.…”
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A Potential Role for HUWE1 in Modulating Cisplatin Sensitivity by Stijn Wenmaekers, Bastiaan J. Viergever, Gunjan Kumar, Onno Kranenburg, Peter C. Black, Mads Daugaard, Richard P. Meijer

“…Recently, a bladder cancer genome-wide CRISPR/Cas9 knock-out screen correlated cisplatin sensitivity to multiple genetic biomarkers. Among the screen’s top hits was the HECT domain-containing ubiquitin E3 ligase (HUWE1). …”
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Proteasome inhibitors block DNA repair and radiosensitize non-small cell lung cancer. by Kyle R Cron, Kaya Zhu, Deepa S Kushwaha, Grace Hsieh, Dmitry Merzon, Jonathan Rameseder, Clark C Chen, Alan D D'Andrea, David Kozono

“…These screens identified several proteasome subunits among top hits, including the topmost hit PSMA1, a component of the core 20 S proteasome. …”
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Classification of non-coding variants with high pathogenic impact. by Lambert Moyon, Camille Berthelot, Alexandra Louis, Nga Thi Thuy Nguyen, Hugues Roest Crollius

“…We applied FINSURF to a diverse set of 30 diseases with described causative non-coding mutations, and correctly identified the disease-causative non-coding variant within the ten top hits in 22 cases. FINSURF is implemented as an online server to as well as custom browser tracks, and provides a quick and efficient solution to prioritize candidate non-coding variants in realistic clinical settings.…”
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A genome-wide linkage and association scan reveals novel loci for autism. by Weiss, L, Arking, D, Daly, M, Chakravarti, A

“…Initial analysis did not yield genome-wide significant associations; however, genotyping of top hits in additional families revealed an SNP on chromosome 5p15 (between SEMA5A and TAS2R1) that was significantly associated with autism (P = 2 x 10(-7)). …”

Computational Screening And In Vitro Study Of Malaysian Plants For Anti Obesity Properties Targeting Pancreatic Lipase by Husain, Nurul Nasuha

“…From the screening results, 13 plants with top hits compounds were identified namely, Momordica charantia, Jatropha curcas, Endiandra kingiana, Calophyllum inophyllum, Garcinia mangostana, Chisocheton ceramicus, Aglaia argentea, Artocarpus champeden, Manilkara zapota, Dysoxylum hainanense, Capsicum annum, Oryza sativa and Hopea hainanensis. …”
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Polymerase ζ Is Involved in Mitochondrial DNA Maintenance Processes in Concert with APE1 Activity by Heike Katrin Schreier, Rahel Stefanie Wiehe, Miria Ricchetti, Lisa Wiesmüller

“…A siRNA screening of literature-based candidates was performed under conditions of enforced oxidative phosphorylation revealing the functional group of polymerases and therein polymerase ζ (POLZ) as top hits. Thus, POLZ knockdown caused mtDNA accumulation, which required the activity of the base excision repair (BER) nuclease APE1, and was followed by compensatory mtDNA replication determined by the single-cell mitochondrial in situ hybridization protocol (mTRIP). …”
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Discovery of coumaric acid derivatives hinted by coastal marine source to seek for uric acid lowering agents by Yu-Shun Yang, Bin Wang, Junzhong Liu, Qin Li, Qin-Cai Jiao, Pei Qin

“…The backbones were derived from the components of coastal marine source Spartina alterniflora and marketed drugs. The top hits Spartinin C10 & C22 suggested high inhibition percentages (78.54 and 93.74) at 10 μM dosage, which were higher than the positive control Allopurinol. …”
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Genome-scale transcriptional activation by an engineered CRISPR-Cas9 complex by Konermann, Silvana, Brigham, Mark D., Trevino, Alexandro E., Joung, Julia, Barcena, Clea, Hsu, Patrick D., Habib, Naomi, Gootenberg, Jonathan S., Nishimasu, Hiroshi, Nureki, Osamu, Zhang, Feng, Abudayyeh, Omar Osama

“…We also synthesized a library consisting of 70,290 guides targeting all human RefSeq coding isoforms to screen for genes that, upon activation, confer resistance to a BRAF inhibitor. The top hits included genes previously shown to be able to confer resistance, and novel candidates were validated using individual sgRNA and complementary DNA overexpression. …”
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