PerkinElmer

Target Discovery

OF

Accurately identify disease-relevant targets and thoroughly validate each one to ensure downstream success in your drug development.

  • Our phenotype-oriented target identification and validation techniques enable direct correlations between genetic alterations and disease phenotypes, reducing the risk of failures at early stages
  • When combined, our in vitro and in vivo methods provide the most accurate prediction of target relevance in human disease
  • Cellular imaging for in vitro target validation
  • In vivo imaging for target discovery
  • Tissue imaging for ex vivo target validation
  • Allow for capture and analysis of all experimental data via our electronic laboratory notebook and data analytic solutions to transform big data into bigger results

Business Insights (16)
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  • Application Note

    NIR Fluorescent Cell Labeling for In Vivo Cell Tracking (VivoTrack 680)

    Fluorescent dyes have been used for many years to label cells for microscopy studies, and a variety of dyes in the visible fluorescence spectrum are available to label different cellular compartments and organelles. Efficient delivery of the fluorophore to the cell without excessively modifying surface proteins or perturbing cell function is the major biotechnological challenge. In addition, researchers have taken on the challenge of in vivo imaging, focusing on near infrared (NIR) dyes that fluoresce in a spectral region better suited for in vivo imaging due to reduced background and higher tissue penetration.

  • Application Note

    Multiplex 2D Imaging of NIR Molecular Imaging Agents on the IVIS SpectrumCT and FMT 4000

    Epifluorescence (2D) imaging of superficially implanted mouse tumor xenograft models offers a fast and simple method for assessing tumor progression or response to therapy. This approach for tumor assessment requires the use of near infrared (NIR) imaging agents specific for different aspects of tumor biology, and this Application Note highlights the ease and utility of multiplex NIR fluorescence imaging to characterize the complex biology within tumors growing in a living mouse.

  • Application Note

    Vascular Imaging Probes For Oncology and Inflammation Using the IVIS Spectrum

    Optical-based in vivo imaging of vascular changes and vascular leak is an emerging modality for studying altered physiology in a variety of different cancers and inflammatory states. A number of fluorescent imaging probes that circulate with the blood, but have no target selectivity, have been used to detect tumor leakiness as an indication of abnormal tumor vasculature. Inflammation is also characterized by distinct vascular changes, including vasodilation and increased vascular permeability, which are induced by the actions of various inflammatory mediators. This process is essential for facilitating access for appropriate cells, cytokines, and other factors to tissue sites in need of healing or protection from infection. This application note investigates the use of three fluorescent imaging probes, to detect and monitor vascular leak and inflammation in preclinical mouse breast cancer models.

  • Application Note

    Imaging Bile Canaliculi in 3D Liver Microtissues using the Opera Phenix HCS System

    Analyzing transport of biliary metabolites is essential to predict pharmacokinetics and hepatotoxicity during drug development. A functional impairment of hepatobilary transporters, such as bile salt export pump (BSEP) and multidrug resistance-associated protein 2 (MRP-2), is strongly associated with an increased risk of cholestatic liver injury. Here, we describe a 3D high-content screening assay to study hepatobiliary transporter function in InSphero human liver microtissues. Confocal imaging and automated image analysis were used to quantify BSEP and MRP-2-mediated efflux of fluorescent substrates into bile canaliculi.

  • Application Note

    Phenotypic Profiling of Autophagy using the Opera Phenix High-Content Screening System

    Cells constantly sense their environment and their response is a spatio-temporal summation of all signals. To maintain physiological stability, cells need to adjust to environmental changes, a process called homeostasis. One of the most important processes involved in maintaining homeostasis is autophagy, and its significance was recognized by the award of the Nobel Prize for Physiology in 2016 to Yoshinori Ohsumi for the discovery of its underlying mechanisms. Although this is not fully understood, it is believed that autophagy can prevent tumor development by degrading, for example, damaged organelles and protein aggregates.

  • Application Note

    Contrast-enhanced Imaging of Vasculature and Soft Tissues Using the Quantum GX MicroCT System

    X-ray CT imaging is commonly used for skeletal imaging as bones are densely mineralized tissues with excellent x-ray attenuation properties. In contrast, soft, less dense tissues often prove to be challenging to image due to their lack of sufficient tissue density. Soft tissues such as muscle, blood vessels and internal organs share similar x-ray attenuation characteristics and are not distinguishable under typical CT settings. In order to introduce density that would improve soft tissue contrast, several contrast agents have been developed for use in clinical and preclinical settings. This application note outlines the use of iodine and nanoparticle-based contrast agents for imaging soft tissues and vasculature in various organs using the Quantum GX to gain further insights into disease and therapeutic response.

  • Application Note

    Stem Cell Research and Regenerative Medicine

    With the potential to treat a wide range of disease, from organ damage to congenital defects, stem cell research and tissue engineering form the underlying basis of regenerative medicine. Significant advances in the science of skin regeneration, for example, have now made it possible to develop and grow artificial skin grafts in a lab for treatment of burn victims. Other therapeutic applications include the use of stem cells to treat and repair central nervous system diseases such as ischemia and cerebral palsy, cardiovascular diseases, as well as autoimmune diseases including type I diabetes.

  • Application Note

    Measuring FRET using the Opera Phenix High-Content Screening System

    Fundamental processes in living cells, such as apoptosis and signal transduction are controlled by proteins, often acting in concert with other protein partners through protein-protein interactions (PPIs). Inappropriate protein-protein recognition can fundamentally contribute to many diseases, including cancer. Therefore, inhibiting protein-protein interactions represents an emerging area in drug design.

  • Application Note

    MicroCT Investigation of Bone Erosion and Deformation in an Osteoarthritic Rat Model

    Osteoarthritis (OA) is the most common form of arthritis and affects a considerable portion of the elderly population. In the U.S., it is estimated that more than 630 million people worldwide have this chronic condition, generally in the knees. OA occurs when the cartilage that cushions the ends of bones within the joints gradually deteriorates, causing synovitis and joint deformation.

    The goal of OA research is to identify new therapeutic strategies that could prevent, reduce, halt progression, or repair the existing damage to the joint. Non-invasive in vivo imaging such as microCT is the standard modality for bone research due to its ability to obtain high-resolution images at an x-ray dose low enough as not to harm the animal. This makes microCT ideal for monitoring disease progression and response to treatments in the same animal over time. However, microCT data visualization and analysis can be cumbersome and time consuming. In this application note, we compared standard microCT software and advanced bone software to investigate bone erosion in an OA rat model.

  • Application Note

    Imaging Hepatocellular Liver Injury using NIR-labeled Annexin V

    Drug induced liver injury (DILI) is a major reason for late stage termination of drug discovery research projects, highlighting the importance of early integration of liver safety assessment in the drug development process. A technical approach for in vivo toxicology determination was developed using Acetaminophen (APAP), a commonly used over-the-counter analgesic and antipyretic drug, to induce acute hepatocellular liver injury.

  • Application Note

    Analyzing ERK Signal Transduction in Live Cells Using a FRET-Based Biosensor

    Extracellular signal-regulated kinase (ERK) is a key component in the regulation of embryogenesis, cell differentiation, cell proliferation, and cell death. The ERK signaling pathway is altered in various cancer types and is frequently investigated as a target for therapeutic intervention. This application note describes how a live cell FRET assay to study ERK signaling was performed on the Operetta CLS™ high-content analysis system. The optimized design of the FRET-based biosensor, the high-quality imaging of the Operetta CLS system and the easy-to-use image analysis tools of the Harmony® software contribute to the robustness of the high-content assay.

  • Application Note

    Phenotypic Analysis of Hypertrophy in Human iPSC-Derived Cardiomyocytes

    Learn how a phenotypic screening assay to study time-dependent effects of endothelin-1-induced hypertrophy was set up using human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes. Learn how: The Opera Phenix system has been applied in the field of neurodegenerative diseases. In this assay, the Opera Phenix system is 4 times faster than the previous Opera® system. Primary neuron morphology is analyzed in a straightforward approach using Harmony software. Careful assay optimization can increase throughput, and minimize the data burden, without compromising assay performance.

  • Application Note

    Preclinical Fluorescence Imaging of Cancer Metastasis to the Lung and Response to Therapy

    Quantitative pre-clinical fluorescence imaging transcends the boundaries of traditional optical imaging of biological structures and physiology by providing information at the molecular level about disease states and therapeutic response. Fluorescent Pre-clinical Imaging Agents and FMT® (Fluorescence Molecular Tomography) Quantitative Pre-clinical Imaging Systems represent powerful tools for research and drug development in the imaging of biological processes and pharmaceutical activity in living animals.

  • Poster

    Molecular imaging of tumor energy metabolism as an early indicator of anti-cancer drug efficacy in small animal models

    Targeted cancer therapy aims to block key signaling pathways that are critical for tumor cell growth and survival. The blockage eventually results in cell death via apoptosis and tumor growth suppression. Encouraged by the success in clinical development, many academic and pharmaceutical researcher are in active pursuit of the improvement of next generation targeted anti-cancer drugs. As a result, many new chemical and biological entities are emerging from initial screening of in vitro, in vitro and/or in silico selection processes. From the perspective of drug development, it poses a great challenge on the next stage of in vivo validation and demands a robust, accurate, and efficient method for assessment of these candidates in living animal models.

  • Poster

    Combined efficacy & toxicity imaging following acute 5-FU treatment of HT-29 tumor xenografts

    Cancer chemotherapy can produce severe side effects such as suppression of immune function and damage to heart muscle, gastrointestinal tract, and liver. If serious enough, tissue injury can be a major reason for late stage termination of drug discovery research projects, so it is becoming more important to integrate safety/toxicology assessments earlier in the drug development process. There are a variety of traditional serum markers, tailored mechanistically to specific tissues, however there are no current non-invasive assessment tools that are capable of looking broadly at in situ biological changes in target and non-target tissue induced by chemical insult.

  • Poster

    In vivo fluorescent imaging of tumor bombesin and transferrin receptor expression as early indicators of sorafenib efficacy in small animal models

    Targeted cancer therapy aims to block key signaling pathways that are critical for tumor cell growth and survival. The blockage eventually results in cell death via apoptosis and eventual tumor growth suppression. This strategy has proven to be quite effective, and the FDA has approved several targeted therapeutics in the past decade. Encouraged by the success in clinical development, many academic and pharmaceutical researchers are in active pursuit of improved next generation targeted anti-cancer drugs. As a result, many new chemical and biological entities are emerging from initial screening of in vitro, in vitro and/or in silico selection processes. From the perspective of drug development, it poses a great challenge for the next stage of in vivo validation and demands a robust, accurate, and efficient method for assessment of these candidates in living animal models.

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