BBB crossing assessment and BBB crossing technologies in CNS Drug Discovery
Publication date: June 2016 Source:Drug Discovery Today: Technologies, Volume 20 Author(s): Pieter J. Gaillard (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - December 13, 2016 Category: Drugs & Pharmacology Source Type: research
Pharmacogenomics in the age of personalized medicine
Publication date: September–December 2016 Source:Drug Discovery Today: Technologies, Volumes 21–22 Author(s): Leslie J. Dickmann, Joseph A. Ware The aim of personalized medicine is to offer the right treatment to the right person at the right dose, thus maximizing efficacy and minimizing toxicity for each individual patient. Pharmacogenomic approaches attempt to refine the aim of personalized medicine by utilizing an individual's germline and somatic DNA signatures to guide treatment. In this review, we highlight the current use of pharmacogenomic based biomarker information in drug labeling. We also present severa...
Source: Drug Discovery Today: Technologies - December 12, 2016 Category: Drugs & Pharmacology Source Type: research
Introduction to the theme ‘technology – translational pharmacology’
Publication date: September–December 2016 Source:Drug Discovery Today: Technologies, Volumes 21–22 Author(s): Saileta Prabhu (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - December 12, 2016 Category: Drugs & Pharmacology Source Type: research
Translational PK/PD modeling to increase probability of success in drug discovery and early development
Publication date: Available online 10 December 2016 Source:Drug Discovery Today: Technologies Author(s): Thierry Lavé, Antonello Caruso, Neil Parrott, Antje Walz In this review we present ways in which translational PK/PD modeling can address opportunities to enhance probability of success in drug discovery and early development. This is achieved by impacting efficacy and safety-driven attrition rates, through increased focus on the quantitative understanding and modeling of translational PK/PD. Application of the proposed principles early in the discovery and development phases is anticipated to bolster confidence ...
Source: Drug Discovery Today: Technologies - December 10, 2016 Category: Drugs & Pharmacology Source Type: research
Cerebral open flow microperfusion (cOFM) an innovative interface to brain tissue
Publication date: Available online 2 December 2016 Source:Drug Discovery Today: Technologies Author(s): Thomas Birngruber, Frank Sinner Cerebral open flow microperfusion (cOFM) is a new in-vivo technique for continuous sampling of the interstitial fluid in brain tissue. cOFM can be used to monitor substance transport across the blood–brain barrier (pharmacokinetics) and to investigate metabolic changes in brain tissue after drug application (pharmacodynamics). The possibility of long-term implantation into the brain makes cOFM an outstanding tool in the development of brain relevant pharmaceutics. (Source: Drug Disco...
Source: Drug Discovery Today: Technologies - December 2, 2016 Category: Drugs & Pharmacology Source Type: research
Quantitative systems pharmacology: a promising approach for translational pharmacology
Publication date: Available online 24 November 2016 Source:Drug Discovery Today: Technologies Author(s): K. Gadkar, D. Kirouac, N. Parrott, S. Ramanujan Biopharmaceutical companies have increasingly been exploring Quantitative Systems Pharmacology (QSP) as a potential avenue to address current challenges in drug development. In this paper, we discuss the application of QSP modeling approaches to address challenges in the translational of preclinical findings to the clinic, a high risk area of drug development. Three cases have been highlighted with QSP models utilized to inform different questions in translational ph...
Source: Drug Discovery Today: Technologies - November 24, 2016 Category: Drugs & Pharmacology Source Type: research
Translational biomarkers: from discovery and development to clinical practice
This article will discuss the current landscape in biomarker research and highlight strategies being adopted to increase the likelihood of transitioning biomarkers from discovery to medical practice to enable more objective decision making, and to improve health outcome. (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - November 19, 2016 Category: Drugs & Pharmacology Source Type: research
Liposome technologies and drug delivery to the CNS
Publication date: Available online 14 November 2016 Source:Drug Discovery Today: Technologies Author(s): Jaap Rip Brain and nervous system disorders represent a large unmet medical need. Central nervous system drug development is hampered by the restricted transport of drugs across the blood–brain barrier. Different strategies to deliver drugs to the brain have been developed. We discuss the current status of development of liposomal drug delivery to the brain. There is a growing interest in targeted delivery of liposomes to the brain and much progress has been made towards successful development of novel treatments f...
Source: Drug Discovery Today: Technologies - November 14, 2016 Category: Drugs & Pharmacology Source Type: research
Modulating the paracellular pathway at the blood –brain barrier: current and future approaches for drug delivery to the CNS
Publication date: Available online 3 November 2016 Source:Drug Discovery Today: Technologies Author(s): Eoin O’Keeffe, Matthew Campbell The blood–brain barrier (BBB) is the tightly regulated point of entry by which any neuro-targeting therapy must pass through. BBB modulation is a means to loosen the size exclusion properties of the barrier by temporarily interfering with the formation of intercellular tight junction (TJ) or adheren junction (AJ) complexes, allowing for diffusion of small molecule therapeutics from blood to brain. Several technologies, such as RNAi, peptidomimetics, high frequency ultrasound and na...
Source: Drug Discovery Today: Technologies - November 3, 2016 Category: Drugs & Pharmacology Source Type: research
Endonuclease mediated genome editing in drug discovery and development: promises and challenges
Publication date: Available online 2 November 2016 Source:Drug Discovery Today: Technologies Author(s): Vidya Prabhu, Han Xu Site specific genome editing has been gradually employed in drug discovery and development process over the past few decades. Recent development of CRISPR technology has significantly accelerated the incorporation of genome editing in the bench side to bedside process. In this review, we summarize examples of applications of genome editing in the drug discovery and development process. We also discuss current hurdles and solutions of genome editing. (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - November 2, 2016 Category: Drugs & Pharmacology Source Type: research
Structural features and inhibitors of bromodomains
Publication date: March 2016 Source:Drug Discovery Today: Technologies, Volume 19 Author(s): Jamel Meslamani, Steven G. Smith, Roberto Sanchez, Ming-Ming Zhou Bromodomains are conserved structural modules responsible for recognizing acetylated-lysine residues on histone tails and other transcription-associated proteins, such as transcription factors and co-factors. Owing to their important functions in the regulation of ordered gene transcription in chromatin, bromodomains of the BET family proteins have recently been shown as druggable targets for a wide array of human diseases, including cancer and inflammation. He...
Source: Drug Discovery Today: Technologies - October 28, 2016 Category: Drugs & Pharmacology Source Type: research
Bromodomains as targets for therapeutic intervention
Publication date: March 2016 Source:Drug Discovery Today: Technologies, Volume 19 Author(s): Steven G. Smith, Ming-Ming Zhou (Source: Drug Discovery Today: Technologies)
Source: Drug Discovery Today: Technologies - October 28, 2016 Category: Drugs & Pharmacology Source Type: research
Altered blood –brain barrier transport in neuro-inflammatory disorders
Publication date: Available online 17 October 2016 Source:Drug Discovery Today: Technologies Author(s): Geert J. Schenk, Helga E. de Vries During neurodegenerative and neuroinflammatory disorders of the central nervous system (CNS), such as Alzheimer's disease (AD) and multiple sclerosis (MS), the protective function of the blood–brain barrier (BBB) may be severely impaired. The general neuro-inflammatory response, ranging from activation of glial cells to immune cell infiltration that is frequently associated with such brain diseases may underlie the loss of the integrity and function of the BBB. Consequentially, th...
Source: Drug Discovery Today: Technologies - October 28, 2016 Category: Drugs & Pharmacology Source Type: research
Translational immunotoxicology of immunomodulatory monoclonal antibodies
Publication date: Available online 19 October 2016 Source:Drug Discovery Today: Technologies Author(s): Frank R. Brennan, Andrea Kiessling While immunomodulatory monoclonal antibodies (mAbs) have a wide therapeutic potential, exaggerated immunopharmacology may drive both acute and delayed immunotoxicity. The existing tools for immunotoxicity assessment do not accurately predict the full range of immunotoxicities observed in humans. New and optimized models, assays, endpoints and biomarkers in animals and humans are required to safeguard patients and allow them access to these often transformational therapies. (Source: ...
Source: Drug Discovery Today: Technologies - October 28, 2016 Category: Drugs & Pharmacology Source Type: research
Measuring blood –brain barrier penetration using the NeuroCart, a CNS test battery
Publication date: Available online 21 October 2016 Source:Drug Discovery Today: Technologies Author(s): Geert Jan Groeneveld, Justin Luke Hay, Johannes Marinus Van Gerven To systematically study the pharmacodynamics of a CNS drug early in the development process, we developed and validated a battery of drug-sensitive CNS tests, which we call NeuroCart. Using this test battery, data-intensive phase 1 studies in healthy subjects can be performed to demonstrate the specific, time- and dose-dependent, neurophysiological and/or neuropsychological effects of a compound, thereby confirming whether the test compound reaches i...
Source: Drug Discovery Today: Technologies - October 28, 2016 Category: Drugs & Pharmacology Source Type: research
