Browsing ICR Divisions by author "Raynaud, Florence"
Now showing items 41-60 of 66
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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 ... -
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 ... -
Metabolomic changes of the multi (-AGC-) kinase inhibitor AT13148 in cells, mice and patients are associated with NOS regulation.
Pal, A; Asad, Y; Ruddle, R; Henley, AT; Swales, K; et al. (SPRINGER, 2020-04-13)INTRODUCTION: To generate biomarkers of target engagement or predictive response for multi-target drugs is challenging. One such compound is the multi-AGC kinase inhibitor AT13148. Metabolic signatures of selective signal ... -
Modulation of Plasma Metabolite Biomarkers of the MAPK Pathway with MEK Inhibitor RO4987655: Pharmacodynamic and Predictive Potential in Metastatic Melanoma.
Ang, JE; Pal, A; Asad, YJ; Henley, AT; Valenti, M; et al. (AMER ASSOC CANCER RESEARCH, 2017-10-01)MAPK pathway activation is frequently observed in human malignancies, including melanoma, and is associated with sensitivity to MEK inhibition and changes in cellular metabolism. Using quantitative mass spectrometry-based ... -
Multiparameter Lead Optimization to Give an Oral Checkpoint Kinase 1 (CHK1) Inhibitor Clinical Candidate: (R)-5-((4-((Morpholin-2-ylmethyl)amino)-5-(trifluoromethyl)pyridin-2-yl)amino)pyrazine-2-carbonitrile (CCT245737).
Osborne, JD; Matthews, TP; McHardy, T; Proisy, N; Cheung, K-MJ; et al. (AMER CHEMICAL SOC, 2016-06-09)Multiparameter optimization of a series of 5-((4-aminopyridin-2-yl)amino)pyrazine-2-carbonitriles resulted in the identification of a potent and selective oral CHK1 preclinical development candidate with in vivo efficacy ... -
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 ... -
p53 Loss in MYC-Driven Neuroblastoma Leads to Metabolic Adaptations Supporting Radioresistance.
Yogev, O; Barker, K; Sikka, A; Almeida, GS; Hallsworth, A; et al. (AMER ASSOC CANCER RESEARCH, 2016-09-29)Neuroblastoma is the most common childhood extracranial solid tumor. In high-risk cases, many of which are characterized by amplification of MYCN, outcome remains poor. Mutations in the p53 (TP53) tumor suppressor are rare ... -
Peritumoral Delivery of Docetaxel-TIPS Microparticles for Prostate Cancer Adjuvant Therapy.
Paliashvili, K; Popov, A; Kalber, TL; Patrick, PS; Hayes, A; et al. (WILEY, 2020-10-19)Recurrence of prostate cancer after radical prostatectomy is a consequence of incomplete tumor resection. Systemic chemotherapy after surgery is associated with significant toxicity. Improved delivery methods for toxic ... -
Phase I Trial of the PARP Inhibitor Olaparib and AKT Inhibitor Capivasertib in Patients with BRCA1/2- and Non-BRCA1/2-Mutant Cancers.
Yap, TA; Kristeleit, R; Michalarea, V; Pettitt, SJ; Lim, JSJ; et al. (AMER ASSOC CANCER RESEARCH, 2020-10-01)Preclinical studies have demonstrated synergy between PARP and PI3K/AKT pathway inhibitors in BRCA1 and BRCA2 (BRCA1/2)-deficient and BRCA1/2-proficient tumors. We conducted an investigator-initiated phase I trial utilizing ... -
Plasma Metabolomic Changes following PI3K Inhibition as Pharmacodynamic Biomarkers: Preclinical Discovery to Phase I Trial Evaluation.
Ang, JE; Pandher, R; Ang, JC; Asad, YJ; Henley, AT; et al. (AMER ASSOC CANCER RESEARCH, 2016-06-01)PI3K plays a key role in cellular metabolism and cancer. Using a mass spectrometry-based metabolomics platform, we discovered that plasma concentrations of 26 metabolites, including amino acids, acylcarnitines, and ... -
Presence of human breast cancer xenograft changes the diurnal profile of amino acids in mice.
Junior, RP; Sonehara, NM; Jardim-Perassi, BV; Pal, A; Asad, Y; et al. (NATURE PORTFOLIO, 2022-01-19)Human xenografts are extremely useful models to study the biology of human cancers and the effects of novel potential therapies. Deregulation of metabolism, including changes in amino acids (AAs), is a common characteristic ... -
Pyrido[3,4-d]pyrimidin-4(3H)-one metabolism mediated by aldehyde oxidase is blocked by C2-substitution.
Hayes, A; Mok, NY; Liu, M; Thai, C; Henley, AT; et al. (TAYLOR & FRANCIS LTD, 2017-09-01)1. We have previously described C8-substituted pyrido[3,4-d]pyrimidin-4(3H)-one derivatives as cell permeable inhibitors of the KDM4 and KDM5 subfamilies of JmjC histone lysine demethylases. 2. Although exemplar compound ... -
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 ... -
Repurposing Vandetanib plus Everolimus for the Treatment of ACVR1-Mutant Diffuse Intrinsic Pontine Glioma.
Carvalho, DM; Richardson, PJ; Olaciregui, N; Stankunaite, R; Lavarino, C; et al. (AMER ASSOC CANCER RESEARCH, 2022-02-01)Somatic mutations in ACVR1 are found in a quarter of children with diffuse intrinsic pontine glioma (DIPG), but there are no ACVR1 inhibitors licensed for the disease. Using an artificial intelligence-based platform to ... -
Signalling involving MET and FAK supports cell division independent of the activity of the cell cycle-regulating CDK4/6 kinases.
Zhang, C; Stockwell, SR; Elbanna, M; Ketteler, R; Freeman, J; et al. (NATURE PUBLISHING GROUP, 2019-07-25)Deregulation of cyclin-dependent kinases 4 and 6 (CDK4/6) is highly prevalent in cancer; yet, inhibitors against these kinases are currently used only in restricted tumour contexts. The extent to which cancers depend on ... -
Structure enabled design of BAZ2-ICR, a chemical probe targeting the bromodomains of BAZ2A and BAZ2B.
Drouin, L; McGrath, S; Vidler, LR; Chaikuad, A; Monteiro, O; et al. (AMER CHEMICAL SOC, 2015-03-12)The bromodomain containing proteins BAZ2A/B play essential roles in chromatin remodeling and regulation of noncoding RNAs. We present the structure based discovery of a potent, selective, and cell active inhibitor 13 ... -
Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening.
Czodrowski, P; Mallinger, A; Wienke, D; Esdar, C; Pöschke, O; et al. (AMER CHEMICAL SOC, 2016-10-27)The mediator complex-associated cyclin dependent kinase CDK8 regulates β-catenin-dependent transcription following activation of WNT signaling. Multiple lines of evidence suggest CDK8 may act as an oncogene in the development ... -
Synthesis and Evaluation of a 2,11-Cembranoid-Inspired Library.
Welford, AJ; Caldwell, JJ; Liu, M; Richards, M; Brown, N; et al. (WILEY-V C H VERLAG GMBH, 2016-04-11)The 2,11-cembranoid family of natural products has been used as inspiration for the synthesis of a structurally simplified, functionally diverse library of octahydroisobenzofuran-based compounds designed to augment a typical ...