Drug discovery is increasingly informed by genomics, which can significantly boost the chances of a novel therapy successfully navigating the lengthy journey from bench to bedside. But despite the rapid proliferation of genomic information, we still have a limited understanding of how specific genes and genetic variations drive tumour growth and therapeutic resistance. In turn, this limits our ability to identify and validate novel targets that are truly informed by biology and make an impact on disease progression – arguably the most crucial step in the whole drug discovery pathway. By Dr Menelas Pangalos & Steve Rees et al. If you'd like to view the original article then follow the link below: https://www.ddw-online.com/therapeutics/p322917-from-genotype-to-phenotype:-leveraging-functional-genomics-in-oncology.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136063/(3)-from-genotype-to-phenotype.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Drug Discovery World - Pharma, Drug Development, Therapeutics, Chemistry & Medicine

From Genotype to Phenotype: Leveraging functional genomics in oncology

Flow cytometry is an invaluable technique for the characterisation of highly heterogeneous cell populations. Thanks to improvements in throughput, automation and multichannel detection capabilities, recent years have seen its use expand across a wide range of drug discovery applications. In this article, we look at novel developments in flow cytometer reagent and instrument design, and what these mean for drug discovery. By Helen Stewart-Miller and Dr Richard Massey If you'd like to view the original article then follow the link below: https://www.ddw-online.com/drug-discovery/p322918-flow-cytometry-the-advanced-systems-overcoming-drug-discovery-pain-points.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136064/(4)-flow-cytometry.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Flow Cytometry - The advanced systems overcoming drug discovery pain points

Despite major investment in the field, few cell therapies have gained regulatory approval with limited commercial success. The success of therapeutic products is defined by three factors: safety, efficacy and scalability. Achieving these for cell therapy presents new challenges; overcoming transplant rejection (and GvHD in the case of immune cells), producing and culturing functional cells and developing an off-the-shelf therapy with a scalable manufacturing process. If you'd like to view the original article then follow the link below: https://www.ddw-online.com/therapeutics/p323014-cell-therapy-falling-short-of-its-potential.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136359/(6)-cell-therapy.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Cell Therapy - Falling short of its potential?

Drug discovery teams combine specialists with in-depth knowledge from a variety of scientific disciplines. Such diversity in thought worlds poses a challenging exercise in cross-disciplinary collaboration and project coordination. Based on a longitudinal field study of five projects in a leading pharmaceutical company, we present a framework outlining the conditions for effective cross-disciplinary collaboration in drug discovery teams. We show that knowledge creation in multidisciplinary teams relies on a combination of formal team structures and informal co-ordination practices. Formal team structures set the boundary conditions for cross-disciplinary co-ordination. By Professor Zeynep Erden, Shiko Ben-Menahem, Georg von Krogh, Andreas Schneider, Guido Koch, and Hans Widmer If you'd like to view the original article then follow the link below: https://www.ddw-online.com/business/p322924-fostering-multidisciplinary-collaboration-in-drug-discovery.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136068/(8)-fostering-multidisciplinary.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Fostering Multidisciplinary Collaboration in Drug Discovery

In this episode, we look at how commercial products and services are facilitating the automation of cell-based assays to advance drug discovery and accelerate the delivery of new medicines to patients. Cell-based assays are vital tools in modern drug discovery. Live cell cultures that replicate in vivo physiological conditions enable more reliable predictions about the safety and efficacy of drugs. Cellular assays have traditionally been complex and labour-intensive, however, automated technologies are now streamlining workflows as well as improving assay precision. By Helen Stewart-Miller and Kate Tointon If you'd like to view the original article then follow the link below: https://www.ddw-online.com/enabling-technologies/p323011-automated-cell-based-assays:-novel-tools-overcome-the-barriers-to-drug-discovery-success.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136356/(3)-automated-cell-based-assays.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Automated Cell-based Assays: Novel tools overcome the barriers to drug discovery success

New immunotherapies that integrate innate and adaptive immune responses may increase efficacy against many cancers, and have the potential to expand the range of tumours and patients that can be treated with immunotherapy. Over the past decade, insights into the molecular mechanisms that cancer cells use to evade T-cells, antibodies/B cells and other adaptive immune defences have revolutionised oncology therapies. New understandings of how cancer evades innate immune defences – including macrophages, dendritic cells (DC) and Natural Killer (NK) cells – suggest a second, and perhaps even more significant, immunotherapy revolution may be at hand. Original article by Dr Mark Chao, Dr Ranjana Advani, and Dr Jens Peter Volkmer If you'd like to view the original article then follow the link below: https://www.ddw-online.com/therapeutics/p322916-knocking-out-cancer-with-a-one-two-punch.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136062/(2)-knocking-out-cancer.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Immunotherapy - Knocking Out Cancer With a One-Two Punch

In terms of consistency, repeatability, known errors and sheer volume, there exists perhaps no better collection of data for computer learning than that emerging from automated processes. Many common lab procedures now run in parallel, miniaturised experiments – DNA synthesis, target screening, organoid culture, genetic analysis, organic reactions, safety assays – which are poised for extensive curation and algorithm development over the next 10 years. This article briefly outlines each area and offers opinions about how close we are to having artificial intelligence (AI), deep learning (DL) or machine learning (ML) influence each scientific domain. Original article by Dr Michael A. Tarselli, Dr Yohann Potier and Dr Alan E. Fletcher If you'd like to view the original article then follow the link below: https://www.ddw-online.com/enabling-technologies/p323010-automating-automation-how-close-are-we-to-artificial-intelligence-impact.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136355/(2)-automating-automation.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Automating Automation - How close are we to Artificial Intelligence impact?

Recently there have been attempts by small-to-medium sized pharmaceutical companies to create in-house, integrated platform-DDD (PD3) capabilities. This strategy does not come without risks, but has quietly been implemented to increase drug candidate efficacy/safety and pipeline numbers. In some cases this has resulted in much-vaunted success, as epitomised by the Moderna IPO in late 2018. Although the complexities of such efforts should not be underestimated, it is clear that the new PD3 business model is being adopted and utilised. We evaluate this new paradigm and discuss the common traits and themes of successful PD3 companies. Original article by Dr Stephen Naylor and Dr Kirkwood A. Pritchard Jr If you'd like to view the original article then follow the link below: https://www.ddw-online.com/business/p322922-integrated-platform-drug-discovery-and-development-companies-part-ii:-comparative-analysis.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136066/(6)-integrated-platform.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Integrated Platform Drug Discovery and Development Companies - Part 3: Comparative analysis

Recently there has been some attempt to amalgamate platform technologies within start-up and earlystage drug discovery and development companies to increase drug candidate pipeline numbers. This strategy does not come without risks, but has quietly been implemented by a number of platform-drug discovery and development (PD3) companies. This episode, part 2 explores this issue and use Moderna Therapeutics as our case study to highlight the limitations and potential impact on company valuation of such an integrated approach. Original article by Dr Urban A. Kiernan and Dr Stephen Naylor If you'd like to view the original article then follow the link below: https://www.ddw-online.com/business/p322578-emerging-paradigm-of-integrated-platform-drug-discovery-and-development-companies.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/133163/(4)-emerging-paradigm-of-integrated-platform-drug-discovery.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Integrated Platform Drug Discovery and Development Companies - Part 2

Technology was lauded as the saviour of the drug discovery and development process during the late 1990s. A myriad of independent companies developed and offered ‘innovative’ tools, technologies and platforms to pharmaceutical companies in order to mitigate the time, cost and risk of developing new therapeutic drugs. However, comparative analysis of FDA-approved New Molecular Entity (NME) and New Therapeutic Biologic (NTB) annual historical numbers announced does not reflect any significant productivity enhancement impact of such efforts. More recently there has been some attempt to amalgamate platform technologies within start-up and earlystage drug discovery and development (DDD) companies to increase drug candidate pipeline numbers. This strategy does not come without risks, but has quietly been implemented by a number of platform-DDD (PD3) companies. Original article by Dr Urban A. Kiernan and Dr Stephen Naylor If you'd like to view the original article then follow the link below: https://www.ddw-online.com/business/p322578-emerging-paradigm-of-integrated-platform-drug-discovery-and-development-companies.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/133163/(4)-emerging-paradigm-of-integrated-platform-drug-discovery.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Integrated Platform Drug Discovery and Development Companies - Part 1

Drug candidates often fail in the clinic for two reasons: they lack efficacy or possess an adverse toxicity profile. These failures can come at a high cost, especially when drug candidates have already progressed along the development pipeline to clinical trial. Advances in three-dimensional (3D) cell culture systems are helping address the above challenges and improve the likelihood of success for pipeline assets. From disease modelling and validation of novel targets to screening for safety and efficacy, 3D cell cultures offer the exciting potential for the development of novel medicines and increased productivity. This episode describes the benefit of 3D cell culture on the drug discovery workflow, with a focus on lead optimisation in which compounds are assessed for their potential metabolic liability and off-target toxicities. The powerful combination of human-induced pluripotent stem cells (HiPSCs) and 3D cell culture systems are also highlighted. Original article by Dr Richard M. Eglen, Dr Feng Li and Dr Tony Frutos If you'd like to view the original article then follow the link below: https://www.ddw-online.com/drug-discovery/p322782-optimising-clinical-leads:-increasing-drug-discovery-success-with-3d-cell-culture-systems.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/135185/(3)-optimising-clinical-leads.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Increasing Drug Discovery Success With 3D Cell Culture Systems

Plants are stationary soldiers. Rooted to one spot, they are not able to chase nutrients or flee from herbivores and pathogens. So in addition to the basic metabolites they synthesise for their survival, they produce a diverse array of organic compounds through specialised biochemical pathways to counterattack threats. Some of these compounds have been found to combat human threats as well, and herbalists have been scouring these palettes of secondary metabolites for their health-promoting properties for centuries. Modern medicine also incorporates plant compounds. Around 80% of the world’s population already relies on ethnobotanical remedies and plant drugs, such as the antineoplastic Taxol, the antimalarial artemisinin, the analgesic codeine, the antidiabetic allicin, and the cardiac depressant quinidine. The high cost of new drugs, unpalatable side-effects and microbial resistance are driving a constant and renewed public interest on alternative and complementary medicine. Yet only a small fraction of the vast diversity of plant metabolism has been explored. Original article by Michelle Vierra, Strategic Marketing Manager at Pacific Biosciences If you'd like to view the original article then follow the link below: https://www.ddw-online.com/drug-discovery/p322923-mining-plant-genomes-a-modern-approach-to-herbal-healing.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/136067/(7)-a-modern-approach.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Mining Plant Genomes - A modern approach to herbal healing

Once the domain of high-throughput screening (HTS) applications, automated liquid handling systems are now used ubiquitously in drug discovery and have been fundamental in increasing throughput, driving efficiencies and improving standards of accuracy and reproducibility in pharmaceutical and biotechnology workflows. This roundtable article considers some of the latest advances in liquid handling technology and the impact they are having on drug discovery. Drug discovery has undergone a revolution over the past two decades, thanks in large part to the widespread adoption of automated liquid handling. Driven by a competitive need to maximise throughput and increase productivity while ensuring the highest levels of accuracy and reproducibility, automated liquid handling systems have been adopted across the entire pharmaceutical and biotechnology pipeline. Original article by Helen Stewart-Miller and Dr Richard Massey If you'd like to view the original article then follow the link below: https://www.ddw-online.com/enabling-technologies/p322781-how-advanced-automated-liquid-handling-systems-are-reshaping-drug-discovery.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/135184/(2)-faster-smaller.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Advanced Automated Liquid Handling Systems – How they are Reshaping Drug Discovery

The safety and efficacy of therapeutic drugs still requires improvement. However, the advent of both systems biology and precision medicine has stimulated a rethink on the process of therapeutic drug design and polypharmacology. More recently, the definition of polypharmacology has morphed to represent therapeutic drugs that have been designed deliberately for multi-targeting that affords beneficial effects to the patient. This emerging effort has been labelled ‘Systems Pharmacology’ and the products are referred to as multi-target or systems pharmacology drugs. This episode is part 2 of 2 episodes and goes into more detail on systems pharmacology, going through definitions, combination therapy vs systems pharmacology drugs, implementation and approaches. Original article by Dr Kirkwood A. Pritchard Jr, Dr Dustin P. Martin and Dr Stephen Naylor If you'd like to view the original article then follow the link below: https://www.ddw-online.com/therapeutics/p322783-perspective-on-systems-pharmacology:-when-multi-targeting-is-advantageous.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/135186/(4)-perspective-on-systems.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Systems Pharmacology - When multi-targeting is advantageous (Part 2 of 2)

The safety and efficacy of therapeutic drugs still requires improvement. However, the advent of both systems biology and precision medicine has stimulated a rethink on the process of therapeutic drug design and polypharmacology. More recently, the definition of polypharmacology has morphed to represent therapeutic drugs that have been designed deliberately for multi-targeting that affords beneficial effects to the patient. This emerging effort has been labelled ‘Systems Pharmacology’ and the products are referred to as multi-target or systems pharmacology drugs. This episode is part 1 of 2 episodes on the topic of systems pharmacology, and covers ­­human complexity, systems biology and precision medicine. Original article by Dr Kirkwood A. Pritchard Jr, Dr Dustin P. Martin and Dr Stephen Naylor If you'd like to view the original article then follow the link below: https://www.ddw-online.com/therapeutics/p322783-perspective-on-systems-pharmacology:-when-multi-targeting-is-advantageous.html You can also download the original article pdf here: https://www.ddw-online.com/media/32/135186/(4)-perspective-on-systems.pdf For more information on Drug Discovery World, head to: https://www.ddw-online.com

Systems Pharmacology - When multi-targeting is advantageous (Part 1 of 2)

Here at Drug Discovery World (DDW) we've been publishing articles written by leading experts in the Drug Discovery, Pharmaceutical, and BioPharmaceutical industries for nearly 20 years. DDW has grown as a quarterly business review of drug discovery and development. However, we realised that for some, it might be easier to listen to our content on the go, so we've created this podcast to allow you to do just that. In our journal and this podcast, we cover topics surrounding: drug discovery; drug development; business; chemistry; enabling technologies; informatics; personalised medicine; screening; therapeutics, and much more. For the podcast we have selected our most recent, relevant and popular articles, so that you can listen to all of the best content from Drug Discovery World on the go. We hope you enjoy.

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Drug Discovery World - Pharma, Drug Development, Therapeutic...

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