Safety screening in early drug discovery: An optimized assay panel
Several factors contribute to the development failure of novel pharmaceuticals, one of the most important being adverse effects in pre-clinical and clinical studies. Early identification of off-target compound activity can reduce safety-related attrition in development. In vitro profiling of drug ca...
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| Published in | Journal of pharmacological and toxicological methods Vol. 99; p. 106609 |
|---|---|
| Main Authors | , , , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Elsevier Inc
01.09.2019
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1056-8719 1873-488X 1873-488X |
| DOI | 10.1016/j.vascn.2019.106609 |
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| Abstract | Several factors contribute to the development failure of novel pharmaceuticals, one of the most important being adverse effects in pre-clinical and clinical studies. Early identification of off-target compound activity can reduce safety-related attrition in development. In vitro profiling of drug candidates against a broad range of targets is an important part of the compound selection process. Many compounds are synthesized during early drug discovery, making it necessary to assess poly-pharmacology at a limited number of targets. This paper describes how a rational, statistical-ranking approach was used to generate a cost-effective, optimized panel of assays that allows selectivity focused structure-activity relationships to be explored for many molecules.
This panel of 50 targets has been used to routinely screen Roche small molecules generated across a diverse range of therapeutic targets. Target hit rates from the Bioprint® database and internal Roche compounds are discussed. We further describe an example of how this panel was used within an anti-infective project to reduce in vivo testing.
To select the optimized panel of targets, IC50 values of compounds in the BioPrint® database were used to identify assay “hits” i.e. IC50 ≤ 1 μM in 123 different in vitro pharmacological assays. If groups of compounds hit the same targets, the target with the higher hit rate was selected, while others were considered redundant. Using a step-wise analysis, an assay panel was identified to maximize diversity and minimize redundancy. Over a five-year period, this panel of 50 off-targets was used to screen ≈1200 compounds synthesized for Roche drug discovery programs. Compounds were initially tested at 10 μM and hit rates generated are reported. Within one project, the number of hits was used to refine the choice of compounds being assessed in vivo.
95% of compounds from the BioPrint® panel were identified within the top 47-ranked assays. Based on this analytical approach and the addition of three targets with established safety concerns, a Roche panel was created for external screening. hERG is screened internally and not included in this analysis. Screening at 10 μM in the Roche panel identified that adenosine A3 and 5HT2B receptors had the highest hit rates (~30%), with 50% of the targets having a hit rate of ≤4%. An anti-infective program identified that a high number of hits in the Roche panel was associated with mortality in 19 mouse tolerability studies. To reduce the severity and number of such studies, future compound selections integrated the panel hit score into the selection process for in vivo studies. It was identified that compounds which hit less targets in the panel and had free plasma exposures of ~2 μM were generally better tolerated.
This paper describes how an optimized panel of 50 assays was selected on the basis of hit similarity at 123 targets. This reduced panel, provides a cost-effective screening panel for assessing compound promiscuity, whilst also including many safety-relevant targets. Frequent use of the panel in early drug discovery has provided promiscuity and safety-relevant information to inform pre-clinical drug development at Roche. |
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| AbstractList | Several factors contribute to the development failure of novel pharmaceuticals, one of the most important being adverse effects in pre-clinical and clinical studies. Early identification of off-target compound activity can reduce safety-related attrition in development. In vitro profiling of drug candidates against a broad range of targets is an important part of the compound selection process. Many compounds are synthesized during early drug discovery, making it necessary to assess poly-pharmacology at a limited number of targets. This paper describes how a rational, statistical-ranking approach was used to generate a cost-effective, optimized panel of assays that allows selectivity focused structure-activity relationships to be explored for many molecules. This panel of 50 targets has been used to routinely screen Roche small molecules generated across a diverse range of therapeutic targets. Target hit rates from the Bioprint® database and internal Roche compounds are discussed. We further describe an example of how this panel was used within an anti-infective project to reduce in vivo testing.
To select the optimized panel of targets, IC
values of compounds in the BioPrint® database were used to identify assay "hits" i.e. IC
≤ 1 μM in 123 different in vitro pharmacological assays. If groups of compounds hit the same targets, the target with the higher hit rate was selected, while others were considered redundant. Using a step-wise analysis, an assay panel was identified to maximize diversity and minimize redundancy. Over a five-year period, this panel of 50 off-targets was used to screen ≈1200 compounds synthesized for Roche drug discovery programs. Compounds were initially tested at 10 μM and hit rates generated are reported. Within one project, the number of hits was used to refine the choice of compounds being assessed in vivo.
95% of compounds from the BioPrint® panel were identified within the top 47-ranked assays. Based on this analytical approach and the addition of three targets with established safety concerns, a Roche panel was created for external screening. hERG is screened internally and not included in this analysis. Screening at 10 μM in the Roche panel identified that adenosine A
and 5HT
receptors had the highest hit rates (~30%), with 50% of the targets having a hit rate of ≤4%. An anti-infective program identified that a high number of hits in the Roche panel was associated with mortality in 19 mouse tolerability studies. To reduce the severity and number of such studies, future compound selections integrated the panel hit score into the selection process for in vivo studies. It was identified that compounds which hit less targets in the panel and had free plasma exposures of ~2 μM were generally better tolerated.
This paper describes how an optimized panel of 50 assays was selected on the basis of hit similarity at 123 targets. This reduced panel, provides a cost-effective screening panel for assessing compound promiscuity, whilst also including many safety-relevant targets. Frequent use of the panel in early drug discovery has provided promiscuity and safety-relevant information to inform pre-clinical drug development at Roche. Several factors contribute to the development failure of novel pharmaceuticals, one of the most important being adverse effects in pre-clinical and clinical studies. Early identification of off-target compound activity can reduce safety-related attrition in development. In vitro profiling of drug candidates against a broad range of targets is an important part of the compound selection process. Many compounds are synthesized during early drug discovery, making it necessary to assess poly-pharmacology at a limited number of targets. This paper describes how a rational, statistical-ranking approach was used to generate a cost-effective, optimized panel of assays that allows selectivity focused structure-activity relationships to be explored for many molecules. This panel of 50 targets has been used to routinely screen Roche small molecules generated across a diverse range of therapeutic targets. Target hit rates from the Bioprint® database and internal Roche compounds are discussed. We further describe an example of how this panel was used within an anti-infective project to reduce in vivo testing.BACKGROUNDSeveral factors contribute to the development failure of novel pharmaceuticals, one of the most important being adverse effects in pre-clinical and clinical studies. Early identification of off-target compound activity can reduce safety-related attrition in development. In vitro profiling of drug candidates against a broad range of targets is an important part of the compound selection process. Many compounds are synthesized during early drug discovery, making it necessary to assess poly-pharmacology at a limited number of targets. This paper describes how a rational, statistical-ranking approach was used to generate a cost-effective, optimized panel of assays that allows selectivity focused structure-activity relationships to be explored for many molecules. This panel of 50 targets has been used to routinely screen Roche small molecules generated across a diverse range of therapeutic targets. Target hit rates from the Bioprint® database and internal Roche compounds are discussed. We further describe an example of how this panel was used within an anti-infective project to reduce in vivo testing.To select the optimized panel of targets, IC50 values of compounds in the BioPrint® database were used to identify assay "hits" i.e. IC50 ≤ 1 μM in 123 different in vitro pharmacological assays. If groups of compounds hit the same targets, the target with the higher hit rate was selected, while others were considered redundant. Using a step-wise analysis, an assay panel was identified to maximize diversity and minimize redundancy. Over a five-year period, this panel of 50 off-targets was used to screen ≈1200 compounds synthesized for Roche drug discovery programs. Compounds were initially tested at 10 μM and hit rates generated are reported. Within one project, the number of hits was used to refine the choice of compounds being assessed in vivo.METHODTo select the optimized panel of targets, IC50 values of compounds in the BioPrint® database were used to identify assay "hits" i.e. IC50 ≤ 1 μM in 123 different in vitro pharmacological assays. If groups of compounds hit the same targets, the target with the higher hit rate was selected, while others were considered redundant. Using a step-wise analysis, an assay panel was identified to maximize diversity and minimize redundancy. Over a five-year period, this panel of 50 off-targets was used to screen ≈1200 compounds synthesized for Roche drug discovery programs. Compounds were initially tested at 10 μM and hit rates generated are reported. Within one project, the number of hits was used to refine the choice of compounds being assessed in vivo.95% of compounds from the BioPrint® panel were identified within the top 47-ranked assays. Based on this analytical approach and the addition of three targets with established safety concerns, a Roche panel was created for external screening. hERG is screened internally and not included in this analysis. Screening at 10 μM in the Roche panel identified that adenosine A3 and 5HT2B receptors had the highest hit rates (~30%), with 50% of the targets having a hit rate of ≤4%. An anti-infective program identified that a high number of hits in the Roche panel was associated with mortality in 19 mouse tolerability studies. To reduce the severity and number of such studies, future compound selections integrated the panel hit score into the selection process for in vivo studies. It was identified that compounds which hit less targets in the panel and had free plasma exposures of ~2 μM were generally better tolerated.RESULTS95% of compounds from the BioPrint® panel were identified within the top 47-ranked assays. Based on this analytical approach and the addition of three targets with established safety concerns, a Roche panel was created for external screening. hERG is screened internally and not included in this analysis. Screening at 10 μM in the Roche panel identified that adenosine A3 and 5HT2B receptors had the highest hit rates (~30%), with 50% of the targets having a hit rate of ≤4%. An anti-infective program identified that a high number of hits in the Roche panel was associated with mortality in 19 mouse tolerability studies. To reduce the severity and number of such studies, future compound selections integrated the panel hit score into the selection process for in vivo studies. It was identified that compounds which hit less targets in the panel and had free plasma exposures of ~2 μM were generally better tolerated.This paper describes how an optimized panel of 50 assays was selected on the basis of hit similarity at 123 targets. This reduced panel, provides a cost-effective screening panel for assessing compound promiscuity, whilst also including many safety-relevant targets. Frequent use of the panel in early drug discovery has provided promiscuity and safety-relevant information to inform pre-clinical drug development at Roche.DISCUSSIONThis paper describes how an optimized panel of 50 assays was selected on the basis of hit similarity at 123 targets. This reduced panel, provides a cost-effective screening panel for assessing compound promiscuity, whilst also including many safety-relevant targets. Frequent use of the panel in early drug discovery has provided promiscuity and safety-relevant information to inform pre-clinical drug development at Roche. Several factors contribute to the development failure of novel pharmaceuticals, one of the most important being adverse effects in pre-clinical and clinical studies. Early identification of off-target compound activity can reduce safety-related attrition in development. In vitro profiling of drug candidates against a broad range of targets is an important part of the compound selection process. Many compounds are synthesized during early drug discovery, making it necessary to assess poly-pharmacology at a limited number of targets. This paper describes how a rational, statistical-ranking approach was used to generate a cost-effective, optimized panel of assays that allows selectivity focused structure-activity relationships to be explored for many molecules.This panel of 50 targets has been used to routinely screen Roche small molecules generated across a diverse range of therapeutic targets. Target hit rates from the Bioprint® database and internal Roche compounds are discussed. We further describe an example of how this panel was used within an anti-infective project to reduce in vivo testing.To select the optimized panel of targets, IC₅₀ values of compounds in the BioPrint® database were used to identify assay “hits” i.e. IC₅₀ ≤ 1 μM in 123 different in vitro pharmacological assays. If groups of compounds hit the same targets, the target with the higher hit rate was selected, while others were considered redundant. Using a step-wise analysis, an assay panel was identified to maximize diversity and minimize redundancy. Over a five-year period, this panel of 50 off-targets was used to screen ≈1200 compounds synthesized for Roche drug discovery programs. Compounds were initially tested at 10 μM and hit rates generated are reported. Within one project, the number of hits was used to refine the choice of compounds being assessed in vivo.95% of compounds from the BioPrint® panel were identified within the top 47-ranked assays. Based on this analytical approach and the addition of three targets with established safety concerns, a Roche panel was created for external screening. hERG is screened internally and not included in this analysis. Screening at 10 μM in the Roche panel identified that adenosine A₃ and 5HT₂B receptors had the highest hit rates (~30%), with 50% of the targets having a hit rate of ≤4%. An anti-infective program identified that a high number of hits in the Roche panel was associated with mortality in 19 mouse tolerability studies. To reduce the severity and number of such studies, future compound selections integrated the panel hit score into the selection process for in vivo studies. It was identified that compounds which hit less targets in the panel and had free plasma exposures of ~2 μM were generally better tolerated.This paper describes how an optimized panel of 50 assays was selected on the basis of hit similarity at 123 targets. This reduced panel, provides a cost-effective screening panel for assessing compound promiscuity, whilst also including many safety-relevant targets. Frequent use of the panel in early drug discovery has provided promiscuity and safety-relevant information to inform pre-clinical drug development at Roche. Several factors contribute to the development failure of novel pharmaceuticals, one of the most important being adverse effects in pre-clinical and clinical studies. Early identification of off-target compound activity can reduce safety-related attrition in development. In vitro profiling of drug candidates against a broad range of targets is an important part of the compound selection process. Many compounds are synthesized during early drug discovery, making it necessary to assess poly-pharmacology at a limited number of targets. This paper describes how a rational, statistical-ranking approach was used to generate a cost-effective, optimized panel of assays that allows selectivity focused structure-activity relationships to be explored for many molecules. This panel of 50 targets has been used to routinely screen Roche small molecules generated across a diverse range of therapeutic targets. Target hit rates from the Bioprint® database and internal Roche compounds are discussed. We further describe an example of how this panel was used within an anti-infective project to reduce in vivo testing. To select the optimized panel of targets, IC50 values of compounds in the BioPrint® database were used to identify assay “hits” i.e. IC50 ≤ 1 μM in 123 different in vitro pharmacological assays. If groups of compounds hit the same targets, the target with the higher hit rate was selected, while others were considered redundant. Using a step-wise analysis, an assay panel was identified to maximize diversity and minimize redundancy. Over a five-year period, this panel of 50 off-targets was used to screen ≈1200 compounds synthesized for Roche drug discovery programs. Compounds were initially tested at 10 μM and hit rates generated are reported. Within one project, the number of hits was used to refine the choice of compounds being assessed in vivo. 95% of compounds from the BioPrint® panel were identified within the top 47-ranked assays. Based on this analytical approach and the addition of three targets with established safety concerns, a Roche panel was created for external screening. hERG is screened internally and not included in this analysis. Screening at 10 μM in the Roche panel identified that adenosine A3 and 5HT2B receptors had the highest hit rates (~30%), with 50% of the targets having a hit rate of ≤4%. An anti-infective program identified that a high number of hits in the Roche panel was associated with mortality in 19 mouse tolerability studies. To reduce the severity and number of such studies, future compound selections integrated the panel hit score into the selection process for in vivo studies. It was identified that compounds which hit less targets in the panel and had free plasma exposures of ~2 μM were generally better tolerated. This paper describes how an optimized panel of 50 assays was selected on the basis of hit similarity at 123 targets. This reduced panel, provides a cost-effective screening panel for assessing compound promiscuity, whilst also including many safety-relevant targets. Frequent use of the panel in early drug discovery has provided promiscuity and safety-relevant information to inform pre-clinical drug development at Roche. |
| ArticleNumber | 106609 |
| Author | Tillier, Fabien Richter, Hans Roberts, Sonia Lerner, Christian Bissantz, Caterina Kansy, Manfred Guba, Wolfgang Fasching, Bernhard Migeon, Jacques Wyler, René Kramer, Christian Mohr, Susanne Gerebtzoff, Grégori Peters, Jens-Uwe Bendels, Stefanie |
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| Cites_doi | 10.2147/OTT.S170138 10.1016/j.vascn.2017.02.020 10.1134/S1607672917020107 10.1016/j.yrtph.2017.05.009 10.1093/molehr/gaz009 10.1177/0192623317690609 10.1016/j.pharmthera.2014.11.016 10.1111/j.1476-5381.2010.01127.x 10.1016/j.coph.2015.01.006 10.1016/j.drudis.2013.11.014 10.1038/nrd3845-c1 10.1016/j.biopha.2018.10.002 10.1038/nrd2199 10.4155/fmc.13.202 10.1038/nrd2132 10.1177/1087057113498418 10.1038/nrd3845 10.1021/acs.chemrestox.5b00396 10.1016/j.bcp.2017.10.016 10.1152/physrev.00024.2016 10.1007/s11936-018-0649-4 10.4155/fmc.09.51 10.2174/1389450120666190527115538 10.1016/j.addr.2016.04.029 10.1016/j.yrtph.2018.04.014 10.1021/acs.chemrestox.5b00260 10.18632/oncotarget.2037 10.1152/physrev.00049.2017 |
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| References_xml | – volume: 98 start-page: 1591 year: 2018 end-page: 1625 ident: bb0015 article-title: Pharmacology of adenosine receptors: The state of the art publication-title: Physiological Reviews – volume: 97 start-page: 1045 year: 2017 end-page: 1087 ident: bb0005 article-title: Membrane and nuclear estrogen receptor alpha actions: From tissue specificity to medical implications publication-title: Physiological Reviews – volume: 148 start-page: 114 year: 2015 end-page: 131 ident: bb0010 article-title: Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases publication-title: Pharmacology & Therapeutics – volume: 11 start-page: 6227 year: 2018 end-page: 6237 ident: bb0030 article-title: Mechanisms, monitoring, and management of tyrosine kinase inhibitors-associated cardiovascular toxicities publication-title: Oncology Targets Therapy – year: 2019 ident: bb0045 article-title: Drug-like properties - concepts, structure, design, and methods from ADME to toxicity optimization – volume: 11 year: 2012 ident: bb0020 article-title: Reducing safety-related drug attrition: The use of in vitro pharmacological profiling publication-title: Nature Reviews Drug Discovery – volume: 147 start-page: 77 year: 2018 end-page: 92 ident: bb0150 article-title: A partnership with the proteasome; the destructive nature of GSK3 publication-title: Biochemical Pharmacology – volume: 97 start-page: 113 year: 2018 end-page: 123 ident: bb0110 article-title: Complex network theory for the identification and assessment of candidate protein targets publication-title: Computers in Biology and Medicine – volume: 96 start-page: 1 year: 2018 end-page: 17 ident: bb0115 article-title: In silico toxicology protocols publication-title: Regulatory Toxicology and Pharmacology – volume: 6 start-page: 295 year: 2014 end-page: 317 ident: bb0155 article-title: Predictive in silico off-target profiling in drug discovery publication-title: Future Medicinal Chemistry – start-page: 128 year: 2015 end-page: 157 ident: bb0170 article-title: Attrition in the pharmaceutical industry: Reasons, implications, and pathways forward – volume: 18 start-page: 947 year: 2013 end-page: 966 ident: bb0060 article-title: Are GPCRs still a source of new targets? publication-title: Journal of Biomolecular Screening – volume: 20 start-page: 53 year: 2018 ident: bb0140 article-title: Cardiotoxicity of novel targeted chemotherapeutic agents publication-title: Current Treatment Options in Cardiovascular Medicine – volume: 1 start-page: 645 year: 2009 end-page: 665 ident: bb0070 article-title: In vitro safety pharmacology profiling: What else beyond hERG? publication-title: Future Medicinal Chemistry – volume: 28 start-page: 1875 year: 2015 end-page: 1887 ident: bb0055 article-title: Large-scale predictive drug safety: From structural alerts to biological mechanisms publication-title: Chemical Research in Toxicology – volume: 29 start-page: 452 year: 2016 end-page: 472 ident: bb0040 article-title: Safety Lead optimization and candidate identification: Integrating new technologies into decision-making publication-title: Chemical Research in Toxicology – volume: 5 start-page: 821 year: 2006 end-page: 834 ident: bb0080 article-title: Drugs, their targets and the nature and number of drug targets publication-title: Nature Reviews Drug Discovery – volume: 5 start-page: 993 year: 2006 end-page: 996 ident: bb0120 article-title: How many drug targets are there? publication-title: Nature Reviews Drug Discovery – volume: Vol. 11 start-page: 1 year: 2014 end-page: 72 ident: bb0085 article-title: Reducing drug attrition – year: 2019 ident: bb0160 article-title: PPARgamma: Potential therapeutic target for ailments beyond diabetes and its natural agonism publication-title: Current Drug Targets – volume: 19 start-page: 341 year: 2014 end-page: 347 ident: bb0145 article-title: Reducing attrition in drug development: Smart loading preclinical safety assessment publication-title: Drug Discovery Today – volume: 21 start-page: 122 year: 2015 end-page: 126 ident: bb0035 article-title: T, AT1 Angiotensin receptors — vascular and renal epithelial pathways for blood pressure regulation publication-title: Current Opinion in Pharmacology – volume: 5 start-page: 2881 year: 2014 end-page: 2911 ident: bb0105 article-title: GSK-3 as potential target for therapeutic intervention in cancer publication-title: Oncotarget – volume: 25 start-page: 171 year: 2019 end-page: 183 ident: bb0050 article-title: Isoform-specific GSK3A activity is negatively correlated with human sperm motility publication-title: Molecular Human Reproduction – volume: 87 start-page: 108 year: 2017 end-page: 126 ident: bb0100 article-title: Potential functional and pathological side effects related to off-target pharmacological activity publication-title: Journal of Pharmacological and Toxicological Methods – volume: 101 start-page: 34 year: 2016 end-page: 41 ident: bb0095 article-title: Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions publication-title: Advanced Drug Delivery Reviews – volume: 45 start-page: 381 year: 2017 end-page: 388 ident: bb0130 article-title: Regulatory forum review*: Utility of in vitro secondary pharmacology data to assess risk of drug-induced valvular heart disease in humans: Regulatory considerations publication-title: Toxicologic Pathology – volume: 473 start-page: 128 year: 2017 end-page: 131 ident: bb0135 article-title: Computer-aided estimation of the hERG-mediated cardiotoxicity risk of potential drug components publication-title: Doklady Biochemistry and Biophysics – volume: 108 start-page: 1565 year: 2018 end-page: 1571 ident: bb0165 article-title: Exploration of the therapeutic aspects of Lck: A kinase target in inflammatory mediated pathological conditions publication-title: Biomedicine & Pharmacotherapy – volume: 6 start-page: 470 year: 2003 end-page: 480 ident: bb0090 article-title: Predicting ADME properties and side effects: The bioPrint approach publication-title: Current Opinion in Drug Discovery & Development – volume: 87 year: 2017 ident: bb0025 article-title: Current nonclinical testing paradigms in support of safe clinical trials: An IQ consortium drusafe perspective publication-title: Regulatory Toxicology and Pharmacology – volume: 162 start-page: 1239 year: 2011 end-page: 1249 ident: bb0075 article-title: Principles of early drug discovery publication-title: British Journal of Pharmacology – volume: 14 year: 2015 ident: bb0125 article-title: Secondary pharmacology data to assess potential off-target activity of new drugs: A regulatory perspective publication-title: Nature Reviews Drug Discovery – volume: 2019 year: 2019 ident: bb0065 article-title: Histamine H3 receptor antagonists/inverse agonists: Where do they go? publication-title: Pharmacology & Therapeutics – volume: 11 start-page: 6227 year: 2018 ident: 10.1016/j.vascn.2019.106609_bb0030 article-title: Mechanisms, monitoring, and management of tyrosine kinase inhibitors-associated cardiovascular toxicities publication-title: Oncology Targets Therapy doi: 10.2147/OTT.S170138 – volume: 2019 year: 2019 ident: 10.1016/j.vascn.2019.106609_bb0065 article-title: Histamine H3 receptor antagonists/inverse agonists: Where do they go? publication-title: Pharmacology & Therapeutics – volume: 87 start-page: 108 year: 2017 ident: 10.1016/j.vascn.2019.106609_bb0100 article-title: Potential functional and pathological side effects related to off-target pharmacological activity publication-title: Journal of Pharmacological and Toxicological Methods doi: 10.1016/j.vascn.2017.02.020 – volume: 473 start-page: 128 issue: 1 year: 2017 ident: 10.1016/j.vascn.2019.106609_bb0135 article-title: Computer-aided estimation of the hERG-mediated cardiotoxicity risk of potential drug components publication-title: Doklady Biochemistry and Biophysics doi: 10.1134/S1607672917020107 – volume: 87 year: 2017 ident: 10.1016/j.vascn.2019.106609_bb0025 article-title: Current nonclinical testing paradigms in support of safe clinical trials: An IQ consortium drusafe perspective publication-title: Regulatory Toxicology and Pharmacology doi: 10.1016/j.yrtph.2017.05.009 – volume: 25 start-page: 171 issue: 4 year: 2019 ident: 10.1016/j.vascn.2019.106609_bb0050 article-title: Isoform-specific GSK3A activity is negatively correlated with human sperm motility publication-title: Molecular Human Reproduction doi: 10.1093/molehr/gaz009 – volume: 45 start-page: 381 issue: 3 year: 2017 ident: 10.1016/j.vascn.2019.106609_bb0130 article-title: Regulatory forum review*: Utility of in vitro secondary pharmacology data to assess risk of drug-induced valvular heart disease in humans: Regulatory considerations publication-title: Toxicologic Pathology doi: 10.1177/0192623317690609 – volume: 148 start-page: 114 year: 2015 ident: 10.1016/j.vascn.2019.106609_bb0010 article-title: Glycogen synthase kinase-3 (GSK3): Regulation, actions, and diseases publication-title: Pharmacology & Therapeutics doi: 10.1016/j.pharmthera.2014.11.016 – year: 2019 ident: 10.1016/j.vascn.2019.106609_bb0045 – volume: 162 start-page: 1239 issue: 6 year: 2011 ident: 10.1016/j.vascn.2019.106609_bb0075 article-title: Principles of early drug discovery publication-title: British Journal of Pharmacology doi: 10.1111/j.1476-5381.2010.01127.x – volume: 21 start-page: 122 year: 2015 ident: 10.1016/j.vascn.2019.106609_bb0035 article-title: T, AT1 Angiotensin receptors — vascular and renal epithelial pathways for blood pressure regulation publication-title: Current Opinion in Pharmacology doi: 10.1016/j.coph.2015.01.006 – start-page: 128 year: 2015 ident: 10.1016/j.vascn.2019.106609_bb0170 – volume: 19 start-page: 341 issue: 3 year: 2014 ident: 10.1016/j.vascn.2019.106609_bb0145 article-title: Reducing attrition in drug development: Smart loading preclinical safety assessment publication-title: Drug Discovery Today doi: 10.1016/j.drudis.2013.11.014 – volume: 14 issue: 4 year: 2015 ident: 10.1016/j.vascn.2019.106609_bb0125 article-title: Secondary pharmacology data to assess potential off-target activity of new drugs: A regulatory perspective publication-title: Nature Reviews Drug Discovery doi: 10.1038/nrd3845-c1 – volume: 108 start-page: 1565 year: 2018 ident: 10.1016/j.vascn.2019.106609_bb0165 article-title: Exploration of the therapeutic aspects of Lck: A kinase target in inflammatory mediated pathological conditions publication-title: Biomedicine & Pharmacotherapy doi: 10.1016/j.biopha.2018.10.002 – volume: 5 start-page: 993 issue: 12 year: 2006 ident: 10.1016/j.vascn.2019.106609_bb0120 article-title: How many drug targets are there? publication-title: Nature Reviews Drug Discovery doi: 10.1038/nrd2199 – volume: 6 start-page: 295 issue: 3 year: 2014 ident: 10.1016/j.vascn.2019.106609_bb0155 article-title: Predictive in silico off-target profiling in drug discovery publication-title: Future Medicinal Chemistry doi: 10.4155/fmc.13.202 – volume: 5 start-page: 821 issue: 10 year: 2006 ident: 10.1016/j.vascn.2019.106609_bb0080 article-title: Drugs, their targets and the nature and number of drug targets publication-title: Nature Reviews Drug Discovery doi: 10.1038/nrd2132 – volume: 18 start-page: 947 issue: 9 year: 2013 ident: 10.1016/j.vascn.2019.106609_bb0060 article-title: Are GPCRs still a source of new targets? publication-title: Journal of Biomolecular Screening doi: 10.1177/1087057113498418 – volume: Vol. 11 start-page: 1 year: 2014 ident: 10.1016/j.vascn.2019.106609_bb0085 – volume: 11 issue: 12 year: 2012 ident: 10.1016/j.vascn.2019.106609_bb0020 article-title: Reducing safety-related drug attrition: The use of in vitro pharmacological profiling publication-title: Nature Reviews Drug Discovery doi: 10.1038/nrd3845 – volume: 29 start-page: 452 issue: 4 year: 2016 ident: 10.1016/j.vascn.2019.106609_bb0040 article-title: Safety Lead optimization and candidate identification: Integrating new technologies into decision-making publication-title: Chemical Research in Toxicology doi: 10.1021/acs.chemrestox.5b00396 – volume: 147 start-page: 77 year: 2018 ident: 10.1016/j.vascn.2019.106609_bb0150 article-title: A partnership with the proteasome; the destructive nature of GSK3 publication-title: Biochemical Pharmacology doi: 10.1016/j.bcp.2017.10.016 – volume: 97 start-page: 1045 issue: 3 year: 2017 ident: 10.1016/j.vascn.2019.106609_bb0005 article-title: Membrane and nuclear estrogen receptor alpha actions: From tissue specificity to medical implications publication-title: Physiological Reviews doi: 10.1152/physrev.00024.2016 – volume: 20 start-page: 53 issue: 7 year: 2018 ident: 10.1016/j.vascn.2019.106609_bb0140 article-title: Cardiotoxicity of novel targeted chemotherapeutic agents publication-title: Current Treatment Options in Cardiovascular Medicine doi: 10.1007/s11936-018-0649-4 – volume: 6 start-page: 470 issue: 4 year: 2003 ident: 10.1016/j.vascn.2019.106609_bb0090 article-title: Predicting ADME properties and side effects: The bioPrint approach publication-title: Current Opinion in Drug Discovery & Development – volume: 97 start-page: 113 year: 2018 ident: 10.1016/j.vascn.2019.106609_bb0110 article-title: Complex network theory for the identification and assessment of candidate protein targets publication-title: Computers in Biology and Medicine – volume: 1 start-page: 645 issue: 4 year: 2009 ident: 10.1016/j.vascn.2019.106609_bb0070 article-title: In vitro safety pharmacology profiling: What else beyond hERG? publication-title: Future Medicinal Chemistry doi: 10.4155/fmc.09.51 – year: 2019 ident: 10.1016/j.vascn.2019.106609_bb0160 article-title: PPARgamma: Potential therapeutic target for ailments beyond diabetes and its natural agonism publication-title: Current Drug Targets doi: 10.2174/1389450120666190527115538 – volume: 101 start-page: 34 year: 2016 ident: 10.1016/j.vascn.2019.106609_bb0095 article-title: Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions publication-title: Advanced Drug Delivery Reviews doi: 10.1016/j.addr.2016.04.029 – volume: 96 start-page: 1 year: 2018 ident: 10.1016/j.vascn.2019.106609_bb0115 article-title: In silico toxicology protocols publication-title: Regulatory Toxicology and Pharmacology doi: 10.1016/j.yrtph.2018.04.014 – volume: 28 start-page: 1875 issue: 10 year: 2015 ident: 10.1016/j.vascn.2019.106609_bb0055 article-title: Large-scale predictive drug safety: From structural alerts to biological mechanisms publication-title: Chemical Research in Toxicology doi: 10.1021/acs.chemrestox.5b00260 – volume: 5 start-page: 2881 issue: 10 year: 2014 ident: 10.1016/j.vascn.2019.106609_bb0105 article-title: GSK-3 as potential target for therapeutic intervention in cancer publication-title: Oncotarget doi: 10.18632/oncotarget.2037 – volume: 98 start-page: 1591 issue: 3 year: 2018 ident: 10.1016/j.vascn.2019.106609_bb0015 article-title: Pharmacology of adenosine receptors: The state of the art publication-title: Physiological Reviews doi: 10.1152/physrev.00049.2017 |
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