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Charlotte Knights
Publications - 13
Citations - 6302
Charlotte Knights is an academic researcher. The author has contributed to research in topics: Cancer & PARP inhibitor. The author has an hindex of 6, co-authored 13 publications receiving 5528 citations.
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Journal ArticleDOI
Targeting the DNA repair defect in BRCA mutant cells as a therapeutic strategy
Hannah Farmer,Nuala McCabe,Christopher J. Lord,Andrew Tutt,Andrew Tutt,Damian A. Johnson,Tobias B. Richardson,Manuela Santarosa,Krystyna J. Dillon,Ian Hickson,Charlotte Knights,Niall M. B. Martin,Stephen P. Jackson,Graeme C. M. Smith,Alan Ashworth +14 more
TL;DR: BRCA1 or BRCA2 dysfunction unexpectedly and profoundly sensitizes cells to the inhibition of PARP enzymatic activity, resulting in chromosomal instability, cell cycle arrest and subsequent apoptosis, illustrating how different pathways cooperate to repair damage.
Journal ArticleDOI
4-[3-(4-cyclopropanecarbonylpiperazine-1-carbonyl)-4-fluorobenzyl]-2H-phthalazin-1-one: a novel bioavailable inhibitor of poly(ADP-ribose) polymerase-1.
Keith Allan Menear,Claire Adcock,Robert Boulter,Xiao-Ling Fan Cockcroft,Louise Copsey,Aaron Cranston,Krystyna J. Dillon,Jan Drzewiecki,Sheila Garman,Sylvie Gomez,Hashim Javaid,Frank Kerrigan,Charlotte Knights,Alan Lau,Vincent Junior Ming-Lai Loh,Ian Timothy William Matthews,Stephen Moore,Mark J. O'Connor,Graeme C. M. Smith,Niall M. B. Martin +19 more
TL;DR: A novel series of substituted 4-benzyl-2 H-phthalazin-1-ones that possess high inhibitory enzyme and cellular potency for both PARP-1 andPARP-2 are disclosed and shows standalone activity against BRCA1-deficient breast cancer cell lines.
Journal ArticleDOI
The PARP Inhibitor AZD2461 Provides Insights into the Role of PARP3 Inhibition for Both Synthetic Lethality and Tolerability with Chemotherapy in Preclinical Models
Lenka Oplustil O'Connor,Stuart L. Rulten,Aaron Cranston,Rajesh Odedra,Henry Brown,Janneke E. Jaspers,Louise J. Jones,Charlotte Knights,Bastiaan Evers,Attilla Ting,Robert Hugh Bradbury,Marina Pajic,Sven Rottenberg,Jos Jonkers,David Alan Rudge,Niall M. B. Martin,Keith W. Caldecott,Alan Lau,Mark J. O'Connor +18 more
TL;DR: The efficacy of AZD2461 is demonstrated against olaparib-resistant tumors that overexpress P-glycoprotein and structural modeling of the PARP3-active site with different PARP inhibitors highlights the potential to develop compounds with differentPARP family member specificity profiles for optimal antitumor activity and tolerability.
Journal ArticleDOI
DNA-dependent protein kinase (DNA-PK) inhibitors. Synthesis and biological activity of quinolin-4-one and pyridopyrimidin-4-one surrogates for the chromen-4-one chemotype.
Celine Cano,Olivier Barbeau,Christine Bailey,Xiao-Ling Fan Cockcroft,Nicola J. Curtin,Heather Mary Ellen Duggan,Mark Frigerio,Bernard T. Golding,Ian R. Hardcastle,Marc Geoffrey Hummersone,Charlotte Knights,Keith Allan Menear,David R. Newell,Caroline Richardson,Graeme C. M. Smith,Ben Spittle,Roger J. Griffin +16 more
TL;DR: Several of the newly synthesized compounds combined high potency against the target enzyme (DNA-PK IC₅₀ = 8 nM) with promising activity as potentiators of ionizing radiation-induced cytotoxicity in vitro, with structure-activity studies indicating that optimal potency resided in pyridopyrimidin-4-ones bearing a substituted dibenzothiophen-1-yl group.
Proceedings ArticleDOI
Abstract B42: ATM deficiency sensitizes gastric cancer cells to the PARP inhibitior olaparib
Xiaoning Guo,Dihan Shen,Wenxiang Cheng,Yu Bai,Xing-Zhi Ni,Dan-ping Shen,Shirong Zhang,Liang Xie,Charlotte Knights,Alan Lau,Mark J. O'Connor,Xiaolu Yin,Anthony Warford,Yi Gu +13 more
TL;DR: In this article, the authors studied the growth inhibitory effects of olaparib (AZD2281) and SN•38 (the active metabolite of Irinotecan) on gastric cancer (GC) cells with reduced ATM expression.