Use of Drug Sensitisers to Improve Therapeutic Index in Cancer

Autor: Yu-Shan Chen, Enhui Jin, Philip J. Day

Publikováno v: Pharmaceutics, Vol 16, Iss 7, p 928 (2024)

The clinical management of malignant tumours is challenging, often leading to severe adverse effects and death. Drug resistance (DR) antagonises the effectiveness of treatments, and increasing drug dosage can worsen the therapeutic index (TI). Curren

Externí odkaz: https://doaj.org/article/fe7c9fbb04af41b2abdb06f234e1e7c3

Involvement of multiple influx and efflux transporters in the accumulation of cationic fluorescent dyes by Escherichia coli

Autor: Srijan Jindal, Lei Yang, Philip J. Day, Douglas B. Kell

Publikováno v: BMC Microbiology, Vol 19, Iss 1, Pp 1-16 (2019)

Abstract Background It is widely believed that most xenobiotics cross biomembranes by diffusing through the phospholipid bilayer, and that the use of protein transporters is an occasional adjunct. According to an alternative view, phospholipid bilaye

Externí odkaz: https://doaj.org/article/92b40ba41ef84a2284ff87153d34d5dc

An untargeted metabolomics strategy to measure differences in metabolite uptake and excretion by mammalian cell lines

Autor: Ivayla Roberts, Steve O'Hagan, Philip J. Day, Marina Wright Muelas, Farah Mughal, Douglas B. Kell

Publikováno v: Wright Muelas, M, Roberts, I, Mughal, F, O’Hagan, S, Day, P J & Kell, D B 2020, ' An untargeted metabolomics strategy to measure differences in metabolite uptake and excretion by mammalian cell lines ', Metabolomics, vol. 16, no. 10, 107 . https://doi.org/10.1007/s11306-020-01725-8
METABOLOMICS
Metabolomics

Introduction It is widely but erroneously believed that drugs get into cells by passing through the phospholipid bilayer portion of the plasma and other membranes. Much evidence shows, however, that this is not the case, and that drugs cross biomembr

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3626df71aff4433dbe754c5f17304dd4
https://doi.org/10.1101/2020.06.02.129239

Exploitation of a Novel Binding Pocket in Human Lipoprotein-Associated Phospholipase A2 (Lp-PLA2) Discovered through X-ray Fragment Screening

Autor: Kirsten V. Smith, Joseph E. Pero, Ralph A. Rivero, Donald O. Somers, Vipulkumar Kantibhai Patel, Agnes C. L. Martin, Rachel McMenamin, Sridhar Aravapalli, Finn P. Holding, Eric S. Manas, Lionel Trottet, Alison Jo-Anne Woolford, Neipp Christopher E, Lydia Y. W. Lee, Ranganadh Velagaleti, Sharna J. Rich, Ren Xie, Peng Li, Glyn Williams, Andrew M. Dodson, Brent W. Mccleland, Lee William Page, Joseph P. Marino, Pascal Grondin, Florent Potvain, Joseph E. Coyle, Christopher William Murray, Philip J. Day, Valerio Berdini

Publikováno v: Journal of Medicinal Chemistry. 59:5356-5367

Elevated levels of human lipoprotein-associated phospholipase A2 (Lp-PLA2) are associated with cardiovascular disease and dementia. A fragment screen was conducted against Lp-PLA2 in order to identify novel inhibitors. Multiple fragment hits were obs

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2d7919286100bbcfc9e76bca6023c7c4
https://doi.org/10.1021/acs.jmedchem.6b00212

Identification of orally bioavailable small-molecule inhibitors of hematopoietic prostaglandin D2 synthase using X-ray fragment based drug discovery

Autor: Joe Coyle, Lee William Page, Dave Clapham, Karen Affleck, Paul N. Mortenson, Jonathan P. Hutchinson, Ashley Paul Hancock, Melanie Leveridge, Joelle Le, Heather Hobbs, David Norton, Rachel McMenamin, Simon Teague, Emma Sherriff, Linda J. Russell, Sorif Uddin, Caroline Richardson, Anne Cleasby, Simon Teanby Hodgson, Philip J. Day, Martyn Frederickson, Gordon Saxty

Publikováno v: Med. Chem. Commun.. 5:134-141

Using X-ray crystallographic screening, fragments 4 and 6 were identified as inhibitors of hematopoietic prostaglandin D2 synthase (H-PGDS). Both fragments induced a small protein movement in the X-ray crystal structure relative to the apo structure,

Externí odkaz: https://explore.openaire.eu/search/publication?articleId=doi_________::3f3850d001e5b02755bbbe21405c11b8
https://doi.org/10.1039/c3md00280b