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Article ; Online: Novel drugs approved by the EMA, the FDA, and the MHRA in 2023: A year in review.

Papapetropoulos, Andreas / Topouzis, Stavros / Alexander, Steve P H / Cortese-Krott, Miriam / Kendall, Dave A / Martemyanov, Kirill A / Mauro, Claudio / Nagercoil, Nithyanandan / Panettieri, Reynold A / Patel, Hemal H / Schulz, Rainer / Stefanska, Barbara / Stephens, Gary J / Teixeira, Mauro M / Vergnolle, Nathalie / Wang, Xin / Ferdinandy, Péter

British journal of pharmacology

2024

Abstract: In 2023, seventy novel drugs received market authorization for the first time in either Europe (by the EMA and the MHRA) or in the United States (by the FDA). Confirming a steady recent trend, more than half of these drugs target rare diseases or ... ...

Abstract	In 2023, seventy novel drugs received market authorization for the first time in either Europe (by the EMA and the MHRA) or in the United States (by the FDA). Confirming a steady recent trend, more than half of these drugs target rare diseases or intractable forms of cancer. Thirty drugs are categorized as "first-in-class" (FIC), illustrating the quality of research and innovation that drives new chemical entity discovery and development. We succinctly describe the mechanism of action of most of these FIC drugs and discuss the therapeutic areas covered, as well as the chemical category to which these drugs belong. The 2023 novel drug list also demonstrates an unabated emphasis on polypeptides (recombinant proteins and antibodies), Advanced Therapy Medicinal Products (gene and cell therapies) and RNA therapeutics, including the first-ever approval of a CRISPR-Cas9-based gene-editing cell therapy.
Language	English
Publishing date	2024-03-22
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.16337
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Article ; Online: Hydroxychloroquine inhibits hemolysis-induced arterial thrombosis ex vivo and improves lung perfusion in hemin-treated mice.

Bourne, Joshua H / Perrella, Gina / El-Awaisi, Juma / Terry, Lauren V / Tinkova, Veronika / Hogg, Rebecca L / Gant, Poppy / Grygielska, Beata / Kalia, Neena / Kavanagh, Dean / Brill, Alexander / Dimitrov, Jordan D / Watson, Steve P / Rayes, Julie

Journal of thrombosis and haemostasis : JTH

2024

Abstract: Background: Free labile hemin acts as a damage-associated molecular pattern during acute and chronic hemolysis and muscle injury supporting platelet activation and thrombosis.: Aim: We investigated the anti-thrombotic potential of hydroxychloroquine ... ...

Abstract	Background: Free labile hemin acts as a damage-associated molecular pattern during acute and chronic hemolysis and muscle injury supporting platelet activation and thrombosis. Aim: We investigated the anti-thrombotic potential of hydroxychloroquine on hemolysis-induced arterial thrombosis ex vivo, hemin-induced platelet activation, ferric-chloride (FeCl Results: Erythrocyte lysis and endothelial cell activation cooperatively supported platelet aggregation and thrombosis at arterial shear stress. This thrombotic effect was reversed by hydroxychloroquine. In a purified system, hydroxychloroquine inhibited platelet build-up on immobilized von Willebrand factor in hemolyzed blood without altering initial platelet recruitment. Hydroxychloroquine inhibited hemin-induced platelet activation and phosphatidylserine exposure independently of reactive oxygen species generation. In the presence of hemin, hydroxychloroquine did not alter glycoprotein VI shedding but reduced C-type-lectin-like-2 expression on platelets. In vivo, hydroxychloroquine reversed pulmonary perfusion decline induced by exogenous administration of hemin. In arterial thrombosis models, hydroxychloroquine inhibited FeCl Conclusion: Hydroxychloroquine inhibited hemolysis-induced arterial thrombosis ex-vivo and improved pulmonary perfusion in hemin-treated mice, supporting a potential benefit of its use as an adjuvant therapy in hemolytic diseases to limit arterial thrombosis and to improve organ perfusion.
Language	English
Publishing date	2024-04-24
Publishing country	England
Document type	Journal Article
ZDB-ID	2112661-6
ISSN	1538-7836 ; 1538-7933
ISSN (online)	1538-7836
ISSN	1538-7933
DOI	10.1016/j.jtha.2024.04.008
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Zs.A 5805: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 295: Show issues

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Article ; Online: Recent changes in the British Journal of Pharmacology: widening scope and improving author and editor experience.

Papapetropoulos, Andreas / Alexander, Steve P H / Cortese-Krott, Miriam / Kendall, Dave A / Martemyanov, Kirill / Mauro, Claudio / Panettieri, Reynold A / Patel, Hemal H / Schulz, Rainer / Stefanska, Barbara / Stephens, Gary J / Teixeira, Mauro M / Vergnolle, Nathalie / Wang, Xin Joy / Ferdinandy, Péter

British journal of pharmacology

2023 Volume 180, Issue 17, Page(s) 2193–2195

Language	English
Publishing date	2023-07-18
Publishing country	England
Document type	Editorial
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/bph.16169
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Article ; Online: Longitudinal assessment of early-life white matter development with quantitative relaxometry in nonhuman primates.

Moody, Jason F / Aggarwal, Nakul / Dean, Douglas C / Tromp, Do P M / Kecskemeti, Steve R / Oler, Jonathan A / Kalin, Ned H / Alexander, Andrew L

NeuroImage

2022 Volume 251, Page(s) 118989

Abstract: Alterations in white matter (WM) development are associated with many neuropsychiatric and neurodevelopmental disorders. Most MRI studies examining WM development employ diffusion tensor imaging (DTI), which relies on estimating diffusion patterns of ... ...

Abstract	Alterations in white matter (WM) development are associated with many neuropsychiatric and neurodevelopmental disorders. Most MRI studies examining WM development employ diffusion tensor imaging (DTI), which relies on estimating diffusion patterns of water molecules as a reflection of WM microstructure. Quantitative relaxometry, an alternative method for characterizing WM microstructural changes, is based on molecular interactions associated with the magnetic relaxation of protons. In a longitudinal study of 34 infant non-human primates (NHP) (Macaca mulatta) across the first year of life, we implement a novel, high-resolution, T1-weighted MPnRAGE sequence to examine WM trajectories of the longitudinal relaxation rate (qR
MeSH term(s)	Animals ; Brain/diagnostic imaging ; Diffusion Tensor Imaging/methods ; Humans ; Longitudinal Studies ; Macaca mulatta ; White Matter/diagnostic imaging
Language	English
Publishing date	2022-02-10
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1147767-2
ISSN	1095-9572 ; 1053-8119
ISSN (online)	1095-9572
ISSN	1053-8119
DOI	10.1016/j.neuroimage.2022.118989
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Zs.A 3664: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 7: Show issues

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Article ; Online: Heme induces human and mouse platelet activation through C-type-lectin-like receptor-2.

Bourne, Joshua H / Colicchia, Martina / Di, Ying / Martin, Eleyna / Slater, Alexander / Roumenina, Lubka T / Dimitrov, Jordan D / Watson, Steve P / Rayes, Julie

Haematologica

2021 Volume 106, Issue 2, Page(s) 626–629

MeSH term(s)	Animals ; Blood Platelets/metabolism ; Carrier Proteins ; Heme ; Humans ; Lectins, C-Type/metabolism ; Membrane Glycoproteins ; Mice ; Platelet Activation ; Platelet Aggregation
Chemical Substances	CLEC-2 protein, mouse ; CLEC2B protein, human ; Carrier Proteins ; Lectins, C-Type ; Membrane Glycoproteins ; Heme (42VZT0U6YR)
Language	English
Publishing date	2021-02-01
Publishing country	Italy
Document type	Letter ; Research Support, Non-U.S. Gov't
ZDB-ID	2333-4
ISSN	1592-8721 ; 0017-6567 ; 0390-6078
ISSN (online)	1592-8721
ISSN	0017-6567 ; 0390-6078
DOI	10.3324/haematol.2020.246488
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Article ; Online: Cannabinoid research in the 2010s.

Maccarrone, Mauro / Alexander, Steve P H

British journal of pharmacology

2012 Volume 165, Issue 8, Page(s) 2409–2410

MeSH term(s)	Biomedical Research ; Cannabinoids/pharmacology ; Congresses as Topic ; Receptors, Cannabinoid/metabolism ; Societies, Scientific
Chemical Substances	Cannabinoids ; Receptors, Cannabinoid
Language	English
Publishing date	2012-03-24
Publishing country	England
Document type	Journal Article
ZDB-ID	80081-8
ISSN	1476-5381 ; 0007-1188
ISSN (online)	1476-5381
ISSN	0007-1188
DOI	10.1111/j.1476-5381.2012.01930.x
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Article ; Online: The dual role of platelet-innate immune cell interactions in thrombo-inflammation.

Rayes, Julie / Bourne, Joshua H / Brill, Alexander / Watson, Steve P

Research and practice in thrombosis and haemostasis

2019 Volume 4, Issue 1, Page(s) 23–35

Abstract: Beyond their role in hemostasis and thrombosis, platelets are increasingly recognized as key regulators of the inflammatory response under sterile and infectious conditions. Both platelet receptors and secretion are critical for these functions and ... ...

Abstract	Beyond their role in hemostasis and thrombosis, platelets are increasingly recognized as key regulators of the inflammatory response under sterile and infectious conditions. Both platelet receptors and secretion are critical for these functions and contribute to their interaction with the endothelium and innate immune system. Platelet-leukocyte interactions are increased in thrombo-inflammatory diseases and are sensitive biomarkers for platelet activation and targets for the development of new therapies. The crosstalk between platelets and innate immune cells promotes thrombosis, inflammation, and tissue damage. However, recent studies have shown that these interactions also regulate the resolution of inflammation, tissue repair, and wound healing. Many of the platelet and leukocyte receptors involved in these bidirectional interactions are not selective for a subset of immune cells. However, specific heterotypic interactions occur in different vascular beds and inflammatory conditions, raising the possibility of disease- and organ-specific pathways of intervention. In this review, we highlight and discuss prominent and emerging interrelationships between platelets and innate immune cells and their dual role in the regulation of the inflammatory response in sterile and infectious thrombo-inflammatory diseases. A better understanding of the functional relevance of these interactions in different vascular beds may provide opportunities for successful therapeutic interventions to regulate the development, progression, and chronicity of various pathological processes.
Language	English
Publishing date	2019-10-17
Publishing country	United States
Document type	Journal Article ; Review
ISSN	2475-0379
ISSN (online)	2475-0379
DOI	10.1002/rth2.12266
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Article ; Online: Spatiotemporal dynamics of nonhuman primate white matter development during the first year of life.

Aggarwal, Nakul / Moody, Jason F / Dean, Douglas C / Tromp, Do P M / Kecskemeti, Steve R / Oler, Jonathan A / Alexander, Andy L / Kalin, Ned H

NeuroImage

2021 Volume 231, Page(s) 117825

Abstract: White matter (WM) development early in life is a critical component of brain development that facilitates the coordinated function of neuronal pathways. Additionally, alterations in WM have been implicated in various neurodevelopmental disorders, ... ...

Abstract	White matter (WM) development early in life is a critical component of brain development that facilitates the coordinated function of neuronal pathways. Additionally, alterations in WM have been implicated in various neurodevelopmental disorders, including psychiatric disorders. Because of the need to understand WM development in the weeks immediately following birth, we characterized changes in WM microstructure throughout the postnatal macaque brain during the first year of life. This is a period in primates during which genetic, developmental, and environmental factors may have long-lasting impacts on WM microstructure. Studies in nonhuman primates (NHPs) are particularly valuable as a model for understanding human brain development because of their evolutionary relatedness to humans. Here, 34 rhesus monkeys (23 females, 11 males) were imaged longitudinally at 3, 7, 13, 25, and 53 weeks of age with T1-weighted (MPnRAGE) and diffusion tensor imaging (DTI). With linear mixed-effects (LME) modeling, we demonstrated robust logarithmic growth in FA, MD, and RD trajectories extracted from 18 WM tracts across the brain. Estimated rate of change curves for FA, MD, and RD exhibited an initial 10-week period of exceedingly rapid WM development, followed by a precipitous decline in growth rates. K-means clustering of raw DTI trajectories and rank ordering of LME model parameters revealed distinct posterior-to-anterior and medial-to-lateral gradients in WM maturation. Finally, we found that individual differences in WM microstructure assessed at 3 weeks of age were significantly related to those at 1 year of age. This study provides a quantitative characterization of very early WM growth in NHPs and lays the foundation for future work focused on the impact of alterations in early WM developmental trajectories in relation to human psychopathology.
MeSH term(s)	Age Factors ; Animals ; Animals, Newborn ; Brain/diagnostic imaging ; Brain/growth & development ; Diffusion Tensor Imaging/methods ; Female ; Imaging, Three-Dimensional/methods ; Macaca mulatta ; Male ; White Matter/diagnostic imaging ; White Matter/growth & development
Language	English
Publishing date	2021-02-05
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	1147767-2
ISSN	1095-9572 ; 1053-8119
ISSN (online)	1095-9572
ISSN	1053-8119
DOI	10.1016/j.neuroimage.2021.117825
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Zs.A 3664: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
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Article ; Online: The Origin of Highly Elevated Cell-Free DNA in Healthy Individuals and Patients with Pancreatic, Colorectal, Lung, or Ovarian Cancer.

Cancer discovery

2023 Volume 13, Issue 10, Page(s) 2166–2179

Abstract: ... Pisareva, p. 2122. This article is featured in Selected Articles from This Issue, p. 2109. ...

Abstract	Cell-free DNA (cfDNA) concentrations from patients with cancer are often elevated compared with those of healthy controls, but the sources of this extra cfDNA have never been determined. To address this issue, we assessed cfDNA methylation patterns in 178 patients with cancers of the colon, pancreas, lung, or ovary and 64 patients without cancer. Eighty-three of these individuals had cfDNA concentrations much greater than those generally observed in healthy subjects. The major contributor of cfDNA in all samples was leukocytes, accounting for ∼76% of cfDNA, with neutrophils predominating. This was true regardless of whether the samples were derived from patients with cancer or the total plasma cfDNA concentration. High levels of cfDNA observed in patients with cancer did not come from either neoplastic cells or surrounding normal epithelial cells from the tumor's tissue of origin. These data suggest that cancers may have a systemic effect on cell turnover or DNA clearance. Significance: The origin of excess cfDNA in patients with cancer is unknown. Using cfDNA methylation patterns, we determined that neither the tumor nor the surrounding normal tissue contributes this excess cfDNA-rather it comes from leukocytes. This finding suggests that cancers have a systemic impact on cell turnover or DNA clearance. See related commentary by Thierry and Pisareva, p. 2122. This article is featured in Selected Articles from This Issue, p. 2109.
MeSH term(s)	Humans ; Female ; Cell-Free Nucleic Acids/genetics ; DNA Methylation ; DNA, Neoplasm/genetics ; Pancreas/pathology ; Ovarian Neoplasms/genetics ; Lung/pathology ; Colorectal Neoplasms/genetics ; Biomarkers, Tumor/genetics
Chemical Substances	Cell-Free Nucleic Acids ; DNA, Neoplasm ; Biomarkers, Tumor
Language	English
Publishing date	2023-08-11
Publishing country	United States
Document type	Journal Article
ZDB-ID	2625242-9
ISSN	2159-8290 ; 2159-8274
ISSN (online)	2159-8290
ISSN	2159-8274
DOI	10.1158/2159-8290.CD-21-1252
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Zs.A 6916: Show issues

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Article ; Online: Indian Hedgehog release from TNF-activated renal epithelia drives local and remote organ fibrosis.

O'Sullivan, Eoin D / Mylonas, Katie J / Xin, Cuiyan / Baird, David P / Carvalho, Cyril / Docherty, Marie-Helena / Campbell, Ross / Matchett, Kylie P / Waddell, Scott H / Walker, Alexander D / Gallagher, Kevin M / Jia, Siyang / Leung, Steve / Laird, Alexander / Wilflingseder, Julia / Willi, Michaela / Reck, Maximilian / Finnie, Sarah / Pisco, Angela /

Gordon-Keylock, Sabrina / Medvinsky, Alexander / Boulter, Luke / Henderson, Neil C / Kirschner, Kristina / Chandra, Tamir / Conway, Bryan R / Hughes, Jeremy / Denby, Laura / Bonventre, Joseph V / Ferenbach, David A

Science translational medicine

2023 Volume 15, Issue 698, Page(s) eabn0736

Abstract: Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney and heart. Glioma-associated oncogene 1 expressing ( ... ...

Abstract	Progressive fibrosis is a feature of aging and chronic tissue injury in multiple organs, including the kidney and heart. Glioma-associated oncogene 1 expressing (Gli1
MeSH term(s)	Animals ; Humans ; Mice ; Fibrosis ; Hedgehog Proteins/metabolism ; Inflammation ; NF-kappa B ; Renal Insufficiency, Chronic ; Tumor Necrosis Factors ; Zinc Finger Protein GLI1
Chemical Substances	Hedgehog Proteins ; NF-kappa B ; Tumor Necrosis Factors ; Zinc Finger Protein GLI1 ; IHH protein, human ; ihh protein, mouse
Language	English
Publishing date	2023-05-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2518854-9
ISSN	1946-6242 ; 1946-6234
ISSN (online)	1946-6242
ISSN	1946-6234
DOI	10.1126/scitranslmed.abn0736
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