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- Claesson, Alf, et al.
(författare)
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On Mechanisms of Reactive Metabolite Formation from Drugs
- 2013
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Ingår i: Mini-Reviews in medical chemistry. - : Bentham Science Publishers Ltd.. - 1389-5575 .- 1875-5607. ; 13:5, s. 720-729
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Tidskriftsartikel (refereegranskat)abstract
- Idiosyncratic adverse drug reactions (IADRs) cause a broad range of clinically severe conditions of which drug induced liver injury (DILI) in particular is one of the most frequent causes of safety-related drug withdrawals. The underlying cause is almost invariably formation of reactive metabolites (RM) which by attacking macromolecules induce organ injuries. Attempts are being made in the pharmaceutical industry to lower the risk of selecting unfit compounds as clinical candidates. Approaches vary but do not seem to be overly successful at the initial design/synthesis stage. We review here the most frequent categories of mechanisms for RM formation and propose that many cases of RMs encountered within early ADME screening can be foreseen by applying chemical and metabolic knowledge. We also mention a web tool, SpotRM, which can be used for efficient look-up and learning about drugs that have recognized IADRs likely caused by RM formation.
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| 4. |
- Hallberg, Mathias
(författare)
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Impact of Anabolic Androgenic Steroids on Neuropeptide Systems
- 2011
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Ingår i: Mini-Reviews in medical chemistry. - : Bentham Science Publishers Ltd.. - 1389-5575 .- 1875-5607. ; 11:5, s. 399-408
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Forskningsöversikt (refereegranskat)abstract
- The abuse of anabolic androgenic steroids (AAS) is relatively widely spread and epidemiological studies in the western countries report a prevalence between 1-5% among males. The impact of these steroids on the strength and muscle mass as well as many of the adverse physical effects that have been observed are well described. Several reports have also revealed severe psychological effects as results of the administration of AAS. Effects such as irritability, aggressiveness, anxiety and depression are reported to be associated with AAS abuse. The mechanistic rationales behind these effects are not well understood. Several systems are likely to be involved, including the monoamine and peptidergic systems. The aim of this review is to highlight the potential role of the neuropeptide systems in the brain with focus on how these systems are affected by repeated administration of AAS.
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| 5. |
- Latini, G, et al.
(författare)
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Endocrine disruptors and human health
- 2010
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Ingår i: Mini reviews in medicinal chemistry. - : Bentham Science Publishers Ltd.. - 1875-5607 .- 1389-5575. ; 10:9, s. 846-855
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Tidskriftsartikel (refereegranskat)
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| 6. |
- Moustafa, Moustafa Sherief, et al.
(författare)
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Chemistry of Heterocyclic Five and Six Membered Enamino Nitriles and Enamino Esters
- 2018
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Ingår i: Mini-Reviews in medical chemistry. - : Bentham Science Publishers Ltd.. - 1389-5575 .- 1875-5607. ; 18:12, s. 992-1007
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Forskningsöversikt (refereegranskat)abstract
- Progress in the chemistry of cyclic enamino-nitriles based on the advanced synthetic methodologies is reported. Due to the recent accomplishment, it becomes possible to reactivate these molecules toward electrophiles, nucleophiles and as electron rich dienes in 2+3 dipolar additions and in 4+2 cycloadditions reactions. Synthesizing the poly functionalized 4H-pyrans and their fused derivatives is a fascinating field with a multitude of biological implications such as antitumor, cardiotonic, hepatoprotective, antihypertensive, antibronchitis, as well antifungal activity. This work was conducted with particular emphasis on reviewing the work done on the cyclic enamines since 1990 up till now in order to highlight in more details the synthetic pathways, interactions and the biological activities, Furthermore; we referred to the recent original data of our group contributions within this field.
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| 7. |
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| 8. |
- Bains, Sandra, et al.
(författare)
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Plastid Molecular Pharming II. Production of Biopharmaceuticals by Plastid Transformation
- 2017
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Ingår i: Mini-Reviews in Medicinal Chemistry. - : Bentham Science Publishers Ltd.. - 1389-5575. ; 17:13, s. 1316-1330
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Tidskriftsartikel (refereegranskat)abstract
- Background: Higher plants have been used in medicine throughout human history. Method: While traditional medicinal uses relied on compounds produced naturally by plants, recent advances have enabled the use of plant-based factories to produce diverse agents including pharmaceuticals, antibiotics, and vaccines. The genes responsible for the production of these substances can be either transiently expressed in plants or integrated into their nuclear genome or plastid genome (plastome) by genetic transformation. This review focuses on the application of plastid transformation of higher plants to produce biopharmaceuticals for human applications that are neither antibiotics nor vaccines. Plastid transformation has several advantages over nuclear transformation and represents a minimal risk of transgene contamination to the environment via pollen grains because plastid genes are in most species normally maternally inherited and thus absent from pollen. Other advantages of sitedirected plastid insertion via homologous recombination include strong gene expression due to the plastid genome's high copy number and resistance to silencing, and the ability to achieve multi-gene expression with a single insertion step. Results: Compared to bacterial systems, plant-based bioreactors offer lower production costs, lower risks of human pathogen contamination, and the possibility of exploiting post-translational modification. Conclusion: Consequently, sustainable plant systems based on different species, plastids, and tissues could become an important source of added value in pharmaceutical production.
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| 10. |
- Johansson, Martin H
(författare)
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Reversible Michael additions: Covalent inhibitors and prodrugs.
- 2012
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Ingår i: Mini-Reviews in Medicinal Chemistry. - 1875-5607. ; 12:13, s. 1330-1344
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Tidskriftsartikel (refereegranskat)abstract
- Covalent inhibition is an efficient molecular mechanism for inhibiting enzymes or modulating the function of proteins and is found in the action of many drugs and biologically active natural products. However, it is has been less appreciated that the formation of covalent bonds can be reversible or irreversible. This review focuses on biologically active compounds that are Michael acceptors and how the reversible nature of the Michael addition reaction influences biological activity and how this can be exploited in designing prodrugs.
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