Browsing Cancer Therapeutics by author "Linardopoulos, Spyridon"
Now showing items 1-7 of 7
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Characterisation of CCT271850, a selective, oral and potent MPS1 inhibitor, used to directly measure in vivo MPS1 inhibition vs therapeutic efficacy.
Faisal, A; Mak, GWY; Gurden, MD; Xavier, CPR; Anderhub, SJ; et al. (NATURE PUBLISHING GROUP, 2017-04-25)BACKGROUND: The main role of the cell cycle is to enable error-free DNA replication, chromosome segregation and cytokinesis. One of the best characterised checkpoint pathways is the spindle assembly checkpoint, which ... -
High Proliferation Rate and a Compromised Spindle Assembly Checkpoint Confers Sensitivity to the MPS1 Inhibitor BOS172722 in Triple-Negative Breast Cancers.
Anderhub, SJ; Mak, GW-Y; Gurden, MD; Faisal, A; Drosopoulos, K; et al. (AMER ASSOC CANCER RESEARCH, 2019-10-01)BOS172722 (CCT289346) is a highly potent, selective, and orally bioavailable inhibitor of spindle assembly checkpoint kinase MPS1. BOS172722 treatment alone induces significant sensitization to death, particularly in highly ... -
Metabolism of the dual FLT-3/Aurora kinase inhibitor CCT241736 in preclinical and human in vitro models: Implication for the choice of toxicology species.
Wood, FL; Shepherd, S; Hayes, A; Liu, M; Grira, K; et al. (ELSEVIER, 2019-11-01)CCT241736 is a dual fms-like tyrosine kinase 3 (FLT3)/Aurora kinase inhibitor in development for the treatment of acute myeloid leukaemia. The successful development of any new drug relies on adequate safety testing including ... -
Quizartinib-resistant FLT3-ITD acute myeloid leukemia cells are sensitive to the FLT3-Aurora kinase inhibitor CCT241736.
Moore, AS; Faisal, A; Mak, GWY; Miraki-Moud, F; Bavetsias, V; et al. (ELSEVIER, 2020-04-14)Internal tandem duplication of FLT3 (FLT3-ITD) is one of the most common somatic mutations in acute myeloid leukemia (AML); it causes constitutive activation of FLT3 kinase and is associated with high relapse rates and ... -
Rapid Discovery of Pyrido[3,4-d]pyrimidine Inhibitors of Monopolar Spindle Kinase 1 (MPS1) Using a Structure-Based Hybridization Approach.
Innocenti, P; Woodward, HL; Solanki, S; Naud, S; Westwood, IM; et al. (AMER CHEMICAL SOC, 2016-04-28)Monopolar spindle 1 (MPS1) plays a central role in the transition of cells from metaphase to anaphase and is one of the main components of the spindle assembly checkpoint. Chromosomally unstable cancer cells rely heavily ... -
RNAi screen reveals synthetic lethality between cyclin G-associated kinase and FBXW7 by inducing aberrant mitoses.
Dolly, SO; Gurden, MD; Drosopoulos, K; Clarke, P; de Bono, J; et al. (NATURE PUBLISHING GROUP, 2017-09-26)BACKGROUND: F-box and WD40 repeat domain-containing 7 (FBXW7) is an E3 ubiquitin ligase involved in the ubiquitination and degradation of multiple oncogenic substrates. The tumour suppressor function is frequently lost in ... -
The discovery of potent ribosomal S6 kinase inhibitors by high-throughput screening and structure-guided drug design.
Couty, S; Westwood, IM; Kalusa, A; Cano, C; Travers, J; et al. (IMPACT JOURNALS LLC, 2013-08-25)The ribosomal P70 S6 kinases play a crucial role in PI3K/mTOR regulated signalling pathways and are therefore potential targets for the treatment of a variety of diseases including diabetes and cancer. In this study we ...