| 1. |
- Galetin, Aleksandra, et al.
(författare)
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Membrane transporters in drug development and as determinants of precision medicine
- 2024
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Ingår i: NATURE REVIEWS DRUG DISCOVERY. - 1474-1776 .- 1474-1784. ; 255–280, s. 255-280
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Forskningsöversikt (refereegranskat)abstract
- The effect of membrane transporters on drug disposition, efficacy and safety is now well recognized. Since the initial publication from the International Transporter Consortium, significant progress has been made in understanding the roles and functions of transporters, as well as in the development of tools and models to assess and predict transporter-mediated activity, toxicity and drug-drug interactions (DDIs). Notable advances include an increased understanding of the effects of intrinsic and extrinsic factors on transporter activity, the application of physiologically based pharmacokinetic modelling in predicting transporter-mediated drug disposition, the identification of endogenous biomarkers to assess transporter-mediated DDIs and the determination of the cryogenic electron microscopy structures of SLC and ABC transporters. This article provides an overview of these key developments, highlighting unanswered questions, regulatory considerations and future directions. Significant progress has been made in understanding the influence of membrane transporters in drug disposition and response. Here, the International Transporter Consortium provides an update on the current status of membrane transporters in drug development and regulatory requirements, discusses recent scientific advances in the field and highlights future directions and unanswered questions.
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| 2. |
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| 3. |
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| 4. |
- Collen, A, et al.
(författare)
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VEGFA mRNA for regenerative treatment of heart failure
- 2022
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Ingår i: Nature reviews. Drug discovery. - : Springer Science and Business Media LLC. - 1474-1784 .- 1474-1776. ; 21:1, s. 79-80
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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| 5. |
- Attwood, Misty M., et al.
(författare)
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Trends in kinase drug discovery : targets, indications and inhibitor design
- 2021
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Ingår i: Nature reviews. Drug discovery. - : Springer Nature. - 1474-1776 .- 1474-1784. ; 20:11, s. 839-861
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Tidskriftsartikel (refereegranskat)abstract
- The FDA approval of imatinib in 2001 was a breakthrough in molecularly targeted cancer therapy and heralded the emergence of kinase inhibitors as a key drug class in the oncology area and beyond. Twenty years on, this article analyses the landscape of approved and investigational therapies that target kinases and trends within it, including the most popular targets of kinase inhibitors and their expanding range of indications. There are currently 71 small-molecule kinase inhibitors (SMKIs) approved by the FDA and an additional 16 SMKIs approved by other regulatory agencies. Although oncology is still the predominant area for their application, there have been important approvals for indications such as rheumatoid arthritis, and one-third of the SMKIs in clinical development address disorders beyond oncology. Information on clinical trials of SMKIs reveals that approximately 110 novel kinases are currently being explored as targets, which together with the approximately 45 targets of approved kinase inhibitors represent only about 30% of the human kinome, indicating that there are still substantial unexplored opportunities for this drug class. We also discuss trends in kinase inhibitor design, including the development of allosteric and covalent inhibitors, bifunctional inhibitors and chemical degraders.
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| 6. |
- Olliver, Marie, et al.
(författare)
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ENABLE : an engine for European antibacterial drug discovery and development
- 2021
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Ingår i: Nature reviews. Drug discovery. - : Springer Nature. - 1474-1776 .- 1474-1784. ; 20:6, s. 407-408
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- ENABLE is an antibacterial drug discovery and development consortium formed as a publicprivate partnership in 2014 as part of the Innovative Medicines Initiative (IMI) New Drugs for Bad Bugs (ND4BB) programme. With the project soon ending, here we provide a brief overview and reflect on its achievements, strengths and weaknesses.
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| 8. |
- Attwood, Misty M., et al.
(författare)
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Soluble ligands as drug targets
- 2020
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Ingår i: Nature reviews. Drug discovery. - : NATURE RESEARCH. - 1474-1776 .- 1474-1784. ; 19:10, s. 695-710
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Forskningsöversikt (refereegranskat)abstract
- Historically, the main classes of drug targets have been receptors, enzymes, ion channels and transporters. However, owing largely to the rise of antibody-based therapies in the past two decades, soluble protein ligands such as inflammatory cytokines have become an increasingly important class of drug targets. In this Review, we analyse drugs targeting ligands that have reached clinical development at some point since 1992. We identify 291 drugs that target 99 unique ligands, and we discuss trends in the characteristics of the ligands, drugs and indications for which they have been tested. In the last 5 years, the number of ligand-targeting drugs approved by the FDA has doubled to 34, while the number of clinically validated ligand targets has doubled to 22. Cytokines and growth factors are the predominant types of targeted ligands (70%), and inflammation and autoimmune disorders, cancer and ophthalmological diseases are the top therapeutic areas for both approved agents and agents in clinical studies, reflecting the central role of cytokine and/or growth factor pathways in such diseases. With the rise of antibody-based therapies in the past two decades, soluble protein ligands such as inflammatory cytokines have become an increasingly important class of drug targets. This Review analyses drugs targeting ligands that have reached clinical development in the past three decades and discusses strategic issues such as the pros and cons of different ligand-targeting therapeutic modalities.
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