PI3Kδ hyper-activation promotes development of B cells that exacerbate Streptococcus pneumoniae infection in an antibody-independent manner

Autor: Anne-Katrien Stark, Anita Chandra, Krishnendu Chakraborty, Rafeah Alam, Valentina Carbonaro, Jonathan Clark, Srividya Sriskantharajah, Glyn Bradley, Alex G. Richter, Edward Banham-Hall, Menna R. Clatworthy, Sergey Nejentsev, J. Nicole Hamblin, Edith M. Hessel, Alison M. Condliffe, Klaus Okkenhaug

Publikováno v: Nature Communications, Vol 9, Iss 1, Pp 1-16 (2018)

Antibody mediated immune responses to Streptococcus pneumoniae are crucial for the immune response to infection. Here the authors show hyper-activation of PI3Kδ promotes development of a subset of B cells that exacerbate infection in an antibody-ind

Externí odkaz: https://doaj.org/article/c9aa4017c3b04e369742fcdb03fa2a6c

Optimization of Orally Bioavailable PI3Kδ Inhibitors and Identification of Vps34 as a Key Selectivity Target

Autor: Giovanna Bergamini, Stefano Livia, Kenneth David Down, Marcus Bantscheff, Nick Barton, Friedrich B M Reinhard, Paola Grandi, Daniel Thomas, David N. Mallett, Paul Martin Gore, Sophie M. Bertrand, Z.A. Henley, Edith M. Hessel, James E. Rowedder, Mark Price, J. Nicole Hamblin, Birgit Dümpelfeld, Augustin Amour, Steve Keeling, Christina Rau, Máire A. Convery, Chris D. Edwards, Jonathan A. Taylor, Paul Rowland, Aoife C. Maxwell

Publikováno v: Journal of Medicinal Chemistry. 63:638-655

Optimization of a lead series of PI3Kδ inhibitors based on a dihydroisobenzofuran core led to the identification of potent, orally bioavailable compound 19. Selectivity profiling of compound 19 showed similar potency for class III PI3K, Vps34, and P

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::ee509ec4ce8051c7f53718e7e95b2637
https://doi.org/10.1021/acs.jmedchem.9b01585

Exploring PI3Kδ Molecular Pathways in Stable COPD and Following an Acute Exacerbation, Two Randomized Controlled Trials

Autor: Ken A. Saunders, Robert Wilson, Wim Vos, Cedric Van Holsbeke, Jan De Backer, Claude Poirier, Glyn Bradley, Ingrid Louise Titlestad, Emily Jarvis, Kieran J. Killian, J. Nicole Hamblin, Stephen Mark, Mark Lennon, Anthony Cahn, Augustin Amour, Rikako Tanaka, Teresa Tang, Edith M. Hessel, David Michalovich, Hannah E Wajdner, J. Mark FitzGerald, Malcolm Begg, Jean Bourbeau, Saki Arai, François Maltais

Publikováno v: International Journal of COPD, Vol Volume 16, Pp 1621-1636 (2021)
Begg, M, Hamblin, J N, Jarvis, E, Bradley, G, Mark, S, Michalovich, D, Lennon, M, Wajdner, H E, Amour, A, Wilson, R, Saunders, K, Tanaka, R, Arai, S, Tang, T, Van Holsbeke, C, De Backer, J, Vos, W, Titlestad, I L, FitzGerald, J M, Killian, K, Bourbeau, J, Poirier, C, Maltais, F, Cahn, A & Hessel, E M 2021, ' Exploring PI3Kδ molecular pathways in stable COPD and following an acute exacerbation, two randomized controlled trials ', International Journal of COPD, vol. 16, pp. 1621-1636 . https://doi.org/10.2147/COPD.S309303
International Journal of Chronic Obstructive Pulmonary Disease

Malcolm Begg,1 J Nicole Hamblin,1 Emily Jarvis,2 Glyn Bradley,3 Stephen Mark,4 David Michalovich,5 Mark Lennon,6 Hannah E Wajdner,5 Augustin Amour,5 Robert Wilson,1 Ken Saunders,5 Rikako Tanaka,7 Saki Arai,7 Teresa Tang,8 Cedric Van Holsbeke,9 Jan De

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::534353e7f13ce5b059238bb5b578407c
https://www.dovepress.com/exploring-pi3k-molecular-pathways-in-stable-copd-and-following-an-acut-peer-reviewed-fulltext-article-COPD

Translation of Inhaled Drug Optimization Strategies into Clinical Pharmacokinetics and Pharmacodynamics Using GSK2292767A, a Novel Inhaled Phosphoinositide 3-Kinase δ Inhibitor

Autor: Malcolm Begg, Eleni Pefani, Jonathan Clark, Carla F. Newman, Miriam Marotti, Martin I. Hingle, Disala Fernando, David N. Mallett, Anthony Cahn, Sorif Uddin, Filzah Ehtesham, Josie Morrell, Robert Wilson, Giovanni Vitulli, J. Nicole Hamblin, Jane Gilbert, Chris D. Edwards, Edith M. Hessel, Andrew W Harrell

Publikováno v: Journal of Pharmacology and Experimental Therapeutics. 369:443-453

This study describes the pharmacokinetic (PK) and pharmaco-dynamic (PD) profile of N-(5-(4-(5-(((2R,6S)-2,6-dimethylmorpholino)methyl)oxazol-2-yl)-1H-indazol-6-yl)-2-methoxypyridin-3-yl)methanesulfonamide (GSK2292767A), a novel low-solubility inhaled

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::7d458b382120aa5c2397a9f4a956bd6f
https://doi.org/10.1124/jpet.119.257311

Safety, Tolerability, and Pharmacokinetics of Single and Repeat Doses of Nemiralisib Administered via the Ellipta Dry Powder Inhaler to Healthy Subjects

Autor: Mickael Montembault, Robert Wilson, Emily Jarvis, J. Nicole Hamblin, Anthony Cahn, Edith M. Hessel

Publikováno v: Clinical Therapeutics. 40:1410-1417

Purpose Novel therapies to treat chronic obstructive pulmonary disease are highly desirable. The safety, tolerability, and pharmacokinetic (PK) parameters of nemiralisib, a phosphoinositide 3-kinase δ inhibitor, administered via the Ellipta dry powd

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::1d34e3006e299c3e7453eb1025dee398
https://doi.org/10.1016/j.clinthera.2018.06.011