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- Ahrén, Bo
(författare)
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Islet G protein-coupled receptors as potential targets for treatment of type 2 diabetes.
- 2009
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Ingår i: Nature Reviews. Drug Discovery. - : Springer Science and Business Media LLC. - 1474-1776 .- 1474-1784. ; 8:5, s. 369-385
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Forskningsöversikt (refereegranskat)abstract
- Islet dysfunction - characterized by a combination of defective insulin secretion, inappropriately high glucagon secretion and reduced beta-cell mass - has a central role in the pathophysiology of type 2 diabetes. Several G protein-coupled receptors (GPCRs) expressed in islet beta-cells are known to be involved in the regulation of islet function, and therefore are potential therapeutic targets. This is evident from the recent success of glucagon-like peptide 1 (GLP1) mimetics and dipeptidyl peptidase 4 (DPP4) inhibitors, which promote activation of the GLP1 receptor to stimulate insulin secretion and inhibit glucagon secretion, and also have the potential to increase beta-cell mass. Other islet beta-cell GPCRs that are involved in the regulation of islet function include the glucose-dependent insulinotropic peptide (GIP) receptor, lipid GPCRs, pleiotropic peptide GPCRs and islet biogenic amine GPCRs. This Review summarizes islet GPCR expression, signalling and function, and highlights their potential as targets for the treatment of type 2 diabetes.
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- 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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- 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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- 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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