Browsing Cancer Therapeutics by author "Burke, Rosemary"
Now showing items 21-34 of 34
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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 ... -
Improved Binding Affinity and Pharmacokinetics Enable Sustained Degradation of BCL6 In Vivo.
Huckvale, R; Harnden, AC; Cheung, K-MJ; Pierrat, OA; Talbot, R; et al. (AMER CHEMICAL SOC, 2022-06-23)The transcriptional repressor BCL6 is an oncogenic driver found to be deregulated in lymphoid malignancies. Herein, we report the optimization of our previously reported benzimidazolone molecular glue-type degrader CCT369260 ... -
Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors.
Vaughan, L; Clarke, PA; Barker, K; Chanthery, Y; Gustafson, CW; et al. (IMPACT JOURNALS LLC, 2016-09-06)MYC oncoproteins deliver a potent oncogenic stimulus in several human cancers, making them major targets for drug development, but efforts to deliver clinically practical therapeutics have not yet been realized. In childhood ... -
Into Deep Water: Optimizing BCL6 Inhibitors by Growing into a Solvated Pocket.
Lloyd, MG; Huckvale, R; Cheung, K-MJ; Rodrigues, MJ; Collie, GW; et al. (AMER CHEMICAL SOC, 2021-12-09)We describe the optimization of modestly active starting points to potent inhibitors of BCL6 by growing into a subpocket, which was occupied by a network of five stably bound water molecules. Identifying potent inhibitors ... -
Investigating the phosphinic acid tripeptide mimetic DG013A as a tool compound inhibitor of the M1-aminopeptidase ERAP1.
Wilding, B; Pasqua, AE; E A Chessum, N; Pierrat, OA; Hahner, T; et al. (PERGAMON-ELSEVIER SCIENCE LTD, 2021-06-15)ERAP1 is a zinc-dependent M1-aminopeptidase that trims lipophilic amino acids from the N-terminus of peptides. Owing to its importance in the processing of antigens and regulation of the adaptive immune response, dysregulation ... -
iTAG an optimized IMiD-induced degron for targeted protein degradation in human and murine cells.
Bouguenina, H; Nicolaou, S; Le Bihan, Y-V; Bowling, EA; Calderon, C; et al. (CELL PRESS, 2023-07-21)To address the limitation associated with degron based systems, we have developed iTAG, a synthetic tag based on IMiDs/CELMoDs mechanism of action that improves and addresses the limitations of both PROTAC and previous ... -
MIR21 Drives Resistance to Heat Shock Protein 90 Inhibition in Cholangiocarcinoma.
Lampis, A; Carotenuto, P; Vlachogiannis, G; Cascione, L; Hedayat, S; et al. (W B SAUNDERS CO-ELSEVIER INC, 2018-03-01)BACKGROUND & AIMS: Cholangiocarcinomas (CCA) are resistant to chemotherapy, so new therapeutic agents are needed. We performed a screen to identify small-molecule compounds that are active against CCAs. Levels of microRNA ... -
Molecular mechanisms of human IRE1 activation through dimerization and ligand binding.
Joshi, A; Newbatt, Y; McAndrew, PC; Stubbs, M; Burke, R; et al. (IMPACT JOURNALS LLC, 2015-05-30)IRE1 transduces the unfolded protein response by splicing XBP1 through its C-terminal cytoplasmic kinase-RNase region. IRE1 autophosphorylation is coupled to RNase activity through formation of a back-to-back dimer, although ... -
Optimizing Shape Complementarity Enables the Discovery of Potent Tricyclic BCL6 Inhibitors.
Davis, OA; Cheung, K-MJ; Brennan, A; Lloyd, MG; Rodrigues, MJ; et al. (AMER CHEMICAL SOC, 2022-06-23)To identify new chemical series with enhanced binding affinity to the BTB domain of B-cell lymphoma 6 protein, we targeted a subpocket adjacent to Val18. With no opportunities for strong polar interactions, we focused on ... -
Patient-derived organoids model treatment response of metastatic gastrointestinal cancers.
Vlachogiannis, G; Hedayat, S; Vatsiou, A; Jamin, Y; Fernández-Mateos, J; et al. (AMER ASSOC ADVANCEMENT SCIENCE, 2018-02-23)Patient-derived organoids (PDOs) have recently emerged as robust preclinical models; however, their potential to predict clinical outcomes in patients has remained unclear. We report on a living biobank of PDOs from ... -
Privileged Structures and Polypharmacology within and between Protein Families.
Meyers, J; Chessum, NEA; Ali, S; Mok, NY; Wilding, B; et al. (AMER CHEMICAL SOC, 2018-12-13)Polypharmacology is often a key contributor to the efficacy of a drug, but is also a potential risk. We investigated two hits discovered via a cell-based phenotypic screen, the CDK9 inhibitor CCT250006 (1) and the pirin ... -
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 ... -
Structural and functional characterisation of human RNA helicase DHX8 provides insights into the mechanism of RNA-stimulated ADP release.
Felisberto-Rodrigues, C; Thomas, JC; McAndrew, C; Le Bihan, Y-V; Burke, R; et al. (PORTLAND PRESS LTD, 2019-09-13)DHX8 is a crucial DEAH-box RNA helicase involved in splicing and required for the release of mature mRNA from the spliceosome. Here, we report the biochemical characterisation of full-length human DHX8 and the catalytically ... -
Targeted therapy for LIMD1-deficient non-small cell lung cancer subtypes.
Davidson, K; Grevitt, P; Contreras-Gerenas, MF; Bridge, KS; Hermida, M; et al. (SPRINGERNATURE, 2021-11-11)An early event in lung oncogenesis is loss of the tumour suppressor gene LIMD1 (LIM domains containing 1); this encodes a scaffold protein, which suppresses tumorigenesis via a number of different mechanisms. Approximately ...