Advances in Predictive Toxicology for Discovery Safety through High Content Screening

被引:16
作者
Persson, Mikael [1 ]
Hornberg, Jorrit J. [1 ]
机构
[1] AstraZeneca R&D Gothenburg, Innovat Med & Early Dev, Drug Safety & Metab, Pepparedsleden 1, S-43183 Molndal, Sweden
关键词
CELL-DERIVED CARDIOMYOCYTES; VITRO MICRONUCLEUS ASSAY; HIGH-THROUGHPUT MEASUREMENT; KINETIC IMAGE CYTOMETRY; INDUCED LIVER-INJURY; IN-VITRO; DRUG DISCOVERY; NEURITE OUTGROWTH; ZEBRAFISH EMBRYOS; RISK-ASSESSMENT;
D O I
10.1021/acs.chemrestox.6b00248
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
High content screening enables parallel acquisition of multiple molecular and cellular readouts. In particular the predictive toxicology field has progressed from the advances in high content screening, as more refined end points that report on cellular health can be studied in combination, at the single cell level, and in relatively high throughput. Here, we discuss how high content screening has become an essential tool for Discovery Safety, the discipline that integrates safety and toxicology in the drug discovery process to identify and mitigate safety concerns with the aim to design drug candidates with a superior safety profile. In addition to customized mechanistic assays to evaluate target safety, routine screening assays can be applied to identify risk factors for frequently occurring organ toxicities. We discuss the current state of high content screening assays for hepatotoxicity, cardiotoxicity, neurotoxicity, nephrotoxicity, and genotoxicity, including recent developments and current advances.
引用
收藏
页码:1998 / 2007
页数:10
相关论文
共 50 条
  • [31] Image Analysis in High Content Screening
    Niederlein, Antje
    Meyenhofer, Felix
    White, Daniel
    Bickle, Marc
    COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, 2009, 12 (09) : 899 - 907
  • [32] High content screening: seeing is believing
    Zanella, Fabian
    Lorens, James B.
    Link, Wolfgang
    TRENDS IN BIOTECHNOLOGY, 2010, 28 (05) : 237 - 245
  • [33] High-content screening for the discovery of pharmacological compounds: advantages, challenges and potential benefits of recent technological developments
    Soleilhac, Emmanuelle
    Nadon, Robert
    Lafanechere, Laurence
    EXPERT OPINION ON DRUG DISCOVERY, 2010, 5 (02) : 135 - 144
  • [34] High-content screening assay-based discovery of paullones as novel podocyte-protective agents
    Lee, Ha Won
    Arif, Ehtesham
    Altintas, Mehmet M.
    Quick, Kevin
    Maheshwari, Shrey
    Plezia, Alexandra
    Mahmood, Aqsa
    Reiser, Jochen
    Nihalani, Deepak
    Gupta, Vineet
    AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY, 2018, 314 (02) : F280 - F292
  • [35] A high content screening assay to predict human drug-induced liver injury during drug discovery
    Persson, Mikael
    Loye, Anni F.
    Mow, Tomas
    Hornberg, Jorrit J.
    JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS, 2013, 68 (03) : 302 - 313
  • [36] Discovery of Novel Integrase Inhibitors Acting outside the Active Site Through High-Throughput Screening
    Aknin, Cindy
    Smith, Elena A.
    Marchand, Christophe
    Andreola, Marie-Line
    Pommier, Yves
    Metifiot, Mathieu
    MOLECULES, 2019, 24 (20):
  • [37] Modeling the mature CNS: A predictive screening platform for neurodegenerative disease drug discovery
    LaBarbera, Kelsie Mozzoni
    Limegrover, Colleen
    Rehak, Courtney
    Yurko, Raymond
    Izzo, Nicholas John
    Knezovich, Nicole
    Watto, Emily
    Waybright, Lora
    Catalano, Susan M.
    JOURNAL OF NEUROSCIENCE METHODS, 2021, 358
  • [38] A high content screening assay for discovery of antimycobacterial compounds based on primary human macrophages infected with virulent Mycobacterium tuberculosis
    Kalsum, Sadaf
    Otrocka, Magdalena
    Andersson, Blanka
    Welin, Amanda
    Schon, Thomas
    Jenmalm-Jensen, Annika
    Lundback, Thomas
    Lerm, Maria
    TUBERCULOSIS, 2022, 135
  • [39] High-throughput screening, metabolomics and drug discovery
    Harrigan, GG
    Yates, LA
    IDRUGS, 2006, 9 (03) : 188 - 192
  • [40] High Throughput Screening for Drug Discovery of Autophagy Modulators
    Shu, Chih-Wen
    Liu, Pei-Feng
    Huang, Chun-Ming
    COMBINATORIAL CHEMISTRY & HIGH THROUGHPUT SCREENING, 2012, 15 (09) : 721 - 729