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SynergyFinder 2.0: visual analytics of multi-drug combination synergies

Aleksandr Ianevski, Anil K Giri, Tero Aittokallio
2020 Nucleic Acids Research  
and exploratory visualization of multi-drug synergy patterns, along with automated outlier detection procedure, extended curve-fitting functionality and statistical analysis of replicate measurements.  ...  Here, we describe the latest version of SynergyFinder (release 2.0), which has extensively been upgraded through the addition of novel features supporting especially higher-order combination data analytics  ...  careful beta-testing of the SynergyFinder release 2.0, and for their valuable suggestions on how to improve the web-tool and make it more user-friendly.  ... 
doi:10.1093/nar/gkaa216 pmid:32246720 pmcid:PMC7319457 fatcat:emgsdi2owbfy7egwcdopxm7nja

SynergyFinder 3.0: an interactive analysis and consensus interpretation of multi-drug synergies across multiple samples

Aleksandr Ianevski, Anil K Giri, Tero Aittokallio
2022 Nucleic Acids Research  
SynergyFinder (https://synergyfinder.fimm.fi) is a free web-application for interactive analysis and visualization of multi-drug combination response data.  ...  Since its first release in 2017, SynergyFinder has become a popular tool for multi-dose combination data analytics, partly because the development of its functionality and graphical interface has been  ...  ACKNOWLEDGEMENTS We thank the users of SynergyFinder for their valuable suggestions and requests regarding further extensions of the web-tool.  ... 
doi:10.1093/nar/gkac382 pmid:35580060 pmcid:PMC9252834 fatcat:b2zgkqooffbhljbkopkkobew74

Supplemental Material - Effect of Diclofenac and Andrographolide Combination on Carrageenan-Induced Paw Edema and Hyperalgesia in Rats

Augustine Tandoh, Cynthia Amaning Danquah, Charles Kwaku Benneh, Donatus Wewura Adongo, Eric Boakye-Gyasi, Eric Woode
2022 Figshare  
Supplemental Material for Effect of Diclofenac and Andrographolide Combination on Carrageenan-Induced Paw Edema and Hyperalgesia in Rats by Augustine Tandoh, Cynthia Amaning Danquah, Charles Kwaku Benneh  ...  SynergyFinder 2.0: visual analytics of multi-drug combination synergies. Nucleic Acids Res, 48(W1), 488-493. doi:10.1093/nar/gkaa216 10.  ...  Visualize dose response data : on iv. Calculate synergy : on c. Samples of table format spread sheets are also provided in SynergyFinder 2.0 4.  ... 
doi:10.25384/sage.19930105.v1 fatcat:pmck5hlxrzeqzlt6e3w46vcpei

Synergistic interferon alpha-based drug combinations inhibit SARS-CoV-2 and other viral infections in vitro [article]

Aleksandr Ianevski, Rouan Yao, Eva Zusinaite, Laura Sandra Lello, Sainan Wang, Eunji Jo, Jaewon Yang, Hilde Lysvand, Kirsti Loseth, Valentyn Oksenych, Tanel Tenson, Marc P. Windisch (+11 others)
2021 bioRxiv   pre-print
The combinations of IFNa with camostat, remdesivir, EIDD-2801, cycloheximide or convalescent serum showed strong synergy and, therefore, effectively inhibited SARS-CoV-2 infection.  ...  Antiviral drugs are powerful tools to combat emerging viral diseases, one of the leading causes of morbidity and mortality in the world.  ...  Aittokallio, SynergyFinder 2.0: visual analytics of multi-619 drug combination synergies. Nucleic Acids Res, 2020. 48(W1): p.  ... 
doi:10.1101/2021.01.05.425331 fatcat:qdcrrtlr6ndrxiaagvjvow3gha

Dual Targeting of FLT3 and LSD1 Disrupts the MYC Super-Enhancer Complex in Acute Myeloid Leukemia [article]

William Montomgery Yashar, Brittany M Smith, Daniel J Coleman, Jake VanCampen, Garth Kong, Jommel Macaraeg, Joseph Estabrook, Emek Demir, Nicola Long, Daniel Bottomly, Shannon K McWeeney, Jeffrey W Tyner (+3 others)
2022 bioRxiv   pre-print
High MYC regulon activity was a predictor of response to the drug combination and RNA-seq on drug-treated AML samples revealed suppression of MYC target genes.  ...  High-resolution, multi-modal epigenetic analyses revealed that combined FLT3 and LSD1 inhibition results in the suppression of MYC-bound promoters and the activation of PU.1-bound enhancers.  ...  SynergyFinder 2.0: visual analytics of multidrug combination synergies. Nucleic Acids Res 48, W488-W493 (2020). 55. Corces, M. R. et al.  ... 
doi:10.1101/2022.01.17.476469 fatcat:ufptizz2rfa5no7djexhdirotq

A Network Polypharmacology Approach to Drug Repurposing for Diffuse Intrinsic Pontine Glioma [article]

Finlay MacLean, Pan Pantziarka, Javad Nazarian, Jabe Wilson
2020 bioRxiv   pre-print
To further understand the regulatory mechanisms of these potential drug combinations, we explored the regulatory action of these drugs upon statistically significant biological processes and molecular  ...  We posit that by using a polypharmacological approach to determine drug combinations that target distinct mechanistic pathways of DIPG, it is more likely that an efficacious treatment will be developed  ...  B) calculated 3D synergy maps, SynergyFinder 2.0: visual analytics of multi-drug combination synergies.  ... 
doi:10.1101/2020.06.14.150714 fatcat:vwknosbe3zduvmhgb7xielo3oe

Hepatitis C Virus Drugs Simeprevir and Grazoprevir Synergize with Remdesivir to Suppress SARS-CoV-2 Replication in Cell Culture [article]

Khushboo Bafna, Kris White, Balasubramanian Harish, Romel Rosales, Theresa A. Ramelot, Thomas B. Acton, Elena Moreno, Thomas Kehrer, Lisa Miorin, Catherine A. Royer, Adolfo García-Sastre, Robert M. Krug (+1 others)
2020 bioRxiv   pre-print
There is a striking structural similarity of the substrate binding clefts of SARS- CoV-2 Mpro and HCV NS3/4A proteases, and virtual docking experiments show that all ten HCV drugs can potentially bind  ...  Seven of these HCV drugs inhibit SARS-CoV-2 Mpro protease activity, while four dock well into the PLpro substrate binding cleft and inhibit PLpro protease activity.  ...  SynergyFinder 2.0: visual analytics of 7 multi-drug combination synergies.  ... 
doi:10.1101/2020.12.13.422511 fatcat:m6mcmsx26vc5bbz5jwtwj7vpsu

Cooperative regulation of coupled oncoprotein translation and stability in triple-negative breast cancer by EGFR and CDK12 [article]

Hazel X. Ang, Natalia Sutiman, Xinyue L. Deng, Luke C. Bartelt, Qiang Chen, Alejandro Barrera, Jiaxing Lin, Jeff Sheng, Ian C. McDowell, Timothy E. Reddy, Christopher V. Nicchitta, Kris C. Wood
2021 bioRxiv   pre-print
A genome-wide CRISPR/Cas9 screen identified the CCR4-NOT complex as a major determinant of sensitivity to the combination therapy whose loss renders 4E-BP1 unresponsive to drug-induced dephosphorylation  ...  Using a candidate drug screen, we discovered that inhibition of CDK12 dramatically sensitizes diverse models of TNBC to EGFR blockade.  ...  ACKNOWLEDGEMENTS We thank the members of the K.C.W. and C.V.N. laboratories as well as Sarah Sammons and James Alvarez for their valuable support and feedback on the manuscript.  ... 
doi:10.1101/2021.03.03.433762 fatcat:evst4yto7bcofney7urvzpmfly

Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19

Britton Boras, Rhys M. Jones, Brandon J. Anson, Dan Arenson, Lisa Aschenbrenner, Malina A. Bakowski, Nathan Beutler, Joseph Binder, Emily Chen, Heather Eng, Holly Hammond, Jennifer Hammond (+40 others)
2021 Nature Communications  
Furthermore, we show that PF-00835231 has additive/synergistic activity in combination with remdesivir.  ...  Here we report, the design and characterization of a phosphate prodrug PF-07304814 to enable the delivery and projected sustained systemic exposure in human of PF-00835231 to inhibit coronavirus family  ...  The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. The study performed in Dr.  ... 
doi:10.1038/s41467-021-26239-2 pmid:34663813 pmcid:PMC8523698 fatcat:df4lcfonorfazfie5ulpyzagay

Targeting Gi/o protein-coupled receptor signaling blocks HER2-induced breast cancer development and enhances HER2-targeted therapy [article]

Cancan Lyu, Yuanchao Ye, Maddison Lensing, Kay-Uwe Wagner, Ronald Weigel, Songhai Chen
2021 bioRxiv   pre-print
G protein coupled receptors (GPCRs) are among the most desirable drug targets for human disease.  ...  In this study, we sought a new way of blocking GPCR activation in HER2+-BC by targeting a subgroup of GPCRs that couple to Gi/o proteins (Gi/o-GPCRs).  ...  SynergyFinder 2.0: visual analytics of multi-drug combination synergies. Nucleic Acids Res. 2020;48(W1):W488-W93. 47. Sakamoto K, Schmidt JW, and Wagner KU.  ... 
doi:10.1101/2021.06.15.448534 fatcat:u7pti34fa5d6pn3fslnzh72htm

Albuca Bracteate Polysaccharides Synergistically Enhance the Anti-Tumor Efficacy of 5-Fluorouracil Against Colorectal Cancer by Modulating β-Catenin Signaling and Intestinal Flora

Xinyu Yuan, Jiao Xue, Yingxia Tan, Qingguo Yang, Ziyan Qin, Xiaodong Bao, Shengkai Li, Liangliang Pan, Ziqing Jiang, Yu Wang, Yongliang Lou, Lei Jiang (+1 others)
2021 Frontiers in Pharmacology  
Therefore, further research on the application of ABP in the development of novel anti-tumor drugs and adjuvant compounds is warranted and could improve the outcomes of CRC patients.  ...  Additionally, treatment with a combination of ABP and 5-FU resulted in better outcomes than treatment with either agent alone.  ...  SynergyFinder 2.0: Visual Analytics of Multi-Drug Combination Synergies.  ... 
doi:10.3389/fphar.2021.736627 pmid:34552494 pmcid:PMC8450769 fatcat:aopaltgpyrckhajfrcsa6daypm

Non-oncology drugs are a source of previously unappreciated anti-cancer activity [article]

Steven M Corsello, Rohith T Nagari, Ryan D Spangler, Jordan Rossen, Mustafa Kocak, Jordan G Bryan, Ranad Humeidi, David Peck, Xiaoyun Wu, Andrew A Tang, Vickie M Wang, Samantha A Bender (+24 others)
2019 bioRxiv   pre-print
, which kills cells with low expression of metallothioneins; and the anti-inflammatory drug tepoxalin, whose killing is dependent on high expression of the multi-drug resistance gene ABCB1.  ...  We found that an unexpectedly large number of non-oncology drugs selectively inhibited subsets of cancer cell lines.  ...  Synergy values for each drug combination and cell line were summarized by the synergy score with highest magnitude across dose combinations (max synergy).  ... 
doi:10.1101/730119 fatcat:dt5nv7vwyzfrzdj3mbb4ii5vym

Chirality and asymmetry increase the potency of candidate ADRM1/RPN13 inhibitors

Ravi K. Anchoori, Logan George, Ssu-Hsueh Tseng, Brandon Lam, Srinidhi Polkampally, Anjali D. Amiano, Palmer Foran, Hannah Tsingine, Harideep Samanapally, Fernanda Carrizo Velasquez, Samarjit Das, Deyin Xing (+5 others)
2021 PLoS ONE  
Indeed, a synergistic cytotoxic response was evident upon treatment of several ovarian cancer cell lines with either cisplatin or doxorubicin and our new candidate iRPN13s, suggesting that such a combination  ...  Consequently, interest is mounting in alternative non-peptide based drugs targeting the proteasome's 19S regulatory particle subunit, including its ubiquitin receptor RPN13.  ...  The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.  ... 
doi:10.1371/journal.pone.0256937 pmid:34506530 pmcid:PMC8432795 fatcat:cikq4lfstvgx3l3ogovursmxya

Abstract

2021 European Journal of Clinical Investigation  
Using this technology one can scan cells to determine which pathways are operative and how the pathway activities change due to genetic alterations, epigenetic gene regulation, and exposure to drugs or  ...  The newest mitochondrial assays measure more than 50 aspects of mitochondrial function, profiling the rates of metabolism of mitochondrial substrates and the sensitivity of metabolism of these substrates  ...  The degree of combination effects was quantified by Chou-Talalay algorithm and verified by using the R-package of the computational tool SynergyFinder.  ... 
doi:10.1111/eci.13567 fatcat:casumfo4afhklgo42swkednpya

Coincident modulation of adenosine receptor and metabotropic glutamate receptor 5

NGUYEN HONG PHUC TRINH
2021
The results suggest combination therapies for a wide range of neurodegenerative disorders may be needed to ensure maximal therapeutic benefits.  ...  This thesis provided better understanding of how glutamate receptors behave differently when activating adenosine receptors in different types of brain cells.  ...  Bliss synergy score was also calculated using SynergyFinder 2.0, an open-source free web application for the analysis of drug combination (562), with default parameters.  ... 
doi:10.26180/15001146.v1 fatcat:45qkdff3bjfplngwxxpb52s7ry