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  • The Promise of Epigenetics in Early Stage Drug Discovery
    Epigenetic targets are exciting to drug discovery scientists because they hold great potential across a wide spectrum of therapeutic areas. The field of epigenetics focuses on the investigation of enzymes that alter gene expression through modification of their target substrates, usually through the addition or removal of methyl or acetyl groups. High-throughput assays to identify agents capable of modifying the action of such enzyme targets has, in the past, proven to be challenging due to the relatively small molecular alterations in addition to the possibility of sequential modifications, leading to multiple end products. As such, high-throughput bioassays that allow the direct, concurrent quantification of multiple modification states are attractive. The RapidFire platform enables high-throughput mass spectrometric analysis of native molecules from in vitro reactions by performing on-line desalting in seconds, as opposed to HPLC, which requires minutes. Moreover, the RapidFire system can be connected to any mass spectrometer providing unparalleled versatility in reaction detection.
  • Integrated Quant / Qual for In-vivo Discovery Bioanalysis using Hybrid Quadrupole-Time-of-Flight Mass Spectrometry
    Ultra high performance liquid chromatography (UHPLC) coupled with orthogonal acceleration hybrid quadrupole-time-of-flight (QqTOF) mass spectrometry is an emerging technique offering new strategies for the efficient screening of new chemical entities (NCE) and related molecules at the early discovery stage within the pharmaceutical industry.
  • Drug Delivery: enabling technology for discovery and development
    The integration of pharmacodynamic and pharmacokinetic parameters in non clinical pharmacology studies is a key aspect in drug discovery for efficacy and safety assessment, in the particular for the translation from the non clinical to the clinical field. Modeling the profile of plasma exposure achieved with the intended therapeutic route often requires the use of intravenous infusion. In addition, in most cases infusion parameters (infusion rate, volume, duration and sequences) need to be customized to achieve the appropriate pattern of plasma drug exposure. When pharmacodynamic parameters are recorded by telemetry, the use of implantable pumps rather than external pumps is necessary to preserve the improvement in physiological data recording offered by telemetry.
  • Part 2: How has HR-MS technology fundamentally changed the way we study drug biotransformation and disposition?
    AB SCIEX is proud to present the 2nd installment of a Global 4-Part Live Webinar Series exploring novel and dynamic workflows for Metabolite Identification & Drug Metabolism solutions as it pertains to the 4 main stages of the drug discovery and development paradigm, Lead Discovery, Late Stage Discovery, Early Development and Late Stage Development. Part 2 of this webinar series will focus on how HRMS technology has fundamentally changed the way metabolite biotransformations are investigated in Lead Discovery.
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  • Emergence of zebrafish models in oncology for validating novel anticancer drug targets and nanomaterials
    The zebrafish (Danio rerio) as an in vivo model organism offers great promise to investigate the molecular mechanisms of diverse human diseases, including cancers, because it constitutes a simple and cost effective animal model for performing some genetic alterations and large-scale experiments with high reproducibility
  • Phenotypic screens as a renewed approach for drug discovery
    Well before molecular target-based drug discovery became popular, phenotypic-based screening strategies were the foundation of pharmaceutical drug discovery (Fig. 1). In the past 25 years, molecular target-based drug screening has become the main drug discovery paradigm used in both the pharmaceutical industry and in academic translational research centers. Recently, however, there appears to be renewed interest in reinventing phenotypic screens for lead discovery
  • Shifting from the single to the multitarget paradigm in drug discovery
    It is currently evident that the concept that one drug acts on a single receptor is not as effective as expected from the reductionism view of the lock and key model. The growing evidence for polypharmacology (i.e. that clinical effects are often because of the interaction of single or multiple drugs with multiple targets) is encouraging the shift to experimental and computational multitarget approaches
  • High-content multiplexed tissue imaging and quantification for cancer drug discovery
    This method to quantify tumor model phenotypes can be useful for cancer drug discovery by increasing the understanding of: (i) tumor models used in efficacy studies, (ii) changes occurring during the growth of the tumor, and (iii) novel mechanisms of actions of cancer therapeutics.
  • Low-dose metronomic chemotherapy: from past experience to new paradigms in the treatment of cancer
    This article summarizes preclinical and clinicalexperience with LDM chemotherapy, emphasizing the potential contribution of this new treatmentmodality to future paradigms in the systemic treatment of patients with cancer.
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