Browsing ICR Divisions by author "Workman, Paul"
Now showing items 21-40 of 63
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The era of high-quality chemical probes.
Licciardello, MP; Workman, P (ROYAL SOC CHEMISTRY, 2022-12-14)Small-molecule chemical probes are among the most important tools to study the function of proteins in cells and organisms. Regrettably, the use of weak and non-selective small molecules has generated an abundance of ... -
Evolution of kinase polypharmacology across HSP90 drug discovery.
Antolin, AA; Clarke, PA; Collins, I; Workman, P; Al-Lazikani, B (CELL PRESS, 2021-10-21)Most small molecules interact with several target proteins but this polypharmacology is seldom comprehensively investigated or explicitly exploited during drug discovery. Here, we use computational and experimental methods ... -
Expanding Chemical Probe Space: Quality Criteria for Covalent and Degrader Probes.
Hartung, IV; Rudolph, J; Mader, MM; Mulder, MPC; Workman, P (AMER CHEMICAL SOC, 2023-07-27)Within druggable target space, new small-molecule modalities, particularly covalent inhibitors and targeted degraders, have expanded the repertoire of medicinal chemists. Molecules with such modes of action have a large ... -
Exploiting Protein Conformational Change to Optimize Adenosine-Derived Inhibitors of HSP70.
Cheeseman, MD; Westwood, IM; Barbeau, O; Rowlands, M; Dobson, S; et al. (AMER CHEMICAL SOC, 2016-05-26)HSP70 is a molecular chaperone and a key component of the heat-shock response. Because of its proposed importance in oncology, this protein has become a popular target for drug discovery, efforts which have as yet brought ... -
From patent to patient: analysing access to innovative cancer drugs.
Sharpe, E; Hoey, R; Yap, C; Workman, P (ELSEVIER SCI LTD, 2020-09-01)Analysis of cancer drugs licensed through the European Medicines Agency (EMA) in 2000-2016 shows that the number of authorisations increased over that timeframe. The median number of licensed drugs each year rose from six ... -
HER3 Is an Actionable Target in Advanced Prostate Cancer.
Gil, V; Miranda, S; Riisnaes, R; Gurel, B; D'Ambrosio, M; et al. (AMER ASSOC CANCER RESEARCH, 2021-12-15)It has been recognized for decades that ERBB signaling is important in prostate cancer, but targeting ERBB receptors as a therapeutic strategy for prostate cancer has been ineffective clinically. However, we show here that ... -
HSF1 Is Essential for Myeloma Cell Survival and A Promising Therapeutic Target.
Fok, JHL; Hedayat, S; Zhang, L; Aronson, LI; Mirabella, F; et al. (AMER ASSOC CANCER RESEARCH, 2018-05-15)Purpose: Myeloma is a plasma cell malignancy characterized by the overproduction of immunoglobulin, and is therefore susceptible to therapies targeting protein homeostasis. We hypothesized that heat shock factor 1 (HSF1) ... -
HSF1 Pathway Inhibitor Clinical Candidate (CCT361814/NXP800) Developed from a Phenotypic Screen as a Potential Treatment for Refractory Ovarian Cancer and Other Malignancies.
Pasqua, AE; Sharp, SY; Chessum, NEA; Hayes, A; Pellegrino, L; et al. (AMER CHEMICAL SOC, 2023-04-27)CCT251236 1, a potent chemical probe, was previously developed from a cell-based phenotypic high-throughput screen (HTS) to discover inhibitors of transcription mediated by HSF1, a transcription factor that supports ... -
Imaging biomarker roadmap for cancer studies.
O'Connor, JPB; Aboagye, EO; Adams, JE; Aerts, HJWL; Barrington, SF; et al. (NATURE PORTFOLIO, 2017-03-01)Imaging biomarkers (IBs) are integral to the routine management of patients with cancer. IBs used daily in oncology include clinical TNM stage, objective response and left ventricular ejection fraction. Other CT, MRI, PET ... -
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 ... -
Inhibitors of cyclin-dependent kinases as cancer therapeutics.
Whittaker, SR; Mallinger, A; Workman, P; Clarke, PA (PERGAMON-ELSEVIER SCIENCE LTD, 2017-05-01)Over the past two decades there has been a great deal of interest in the development of inhibitors of the cyclin-dependent kinases (CDKs). This attention initially stemmed from observations that different CDK isoforms have ... -
Minimizing bias in target selection by exploiting multidisciplinary Big Data and the protein interactome.
Al-Lazikani, B; Workman, P (FUTURE SCI LTD, 2016-09-01) -
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 ... -
Modulation of Biliary Cancer Chemo-Resistance Through MicroRNA-Mediated Rewiring of the Expansion of CD133+ Cells.
Carotenuto, P; Hedayat, S; Fassan, M; Cardinale, V; Lampis, A; et al. (LIPPINCOTT WILLIAMS & WILKINS, 2020-09-10)BACKGROUND AND AIMS: Changes in single microRNA (miRNA) expression have been associated with chemo-resistance in biliary tract cancers (BTCs). However, a global assessment of the dynamic role of the microRNome has never ... -
Modulation of pancreatic cancer cell sensitivity to FOLFIRINOX through microRNA-mediated regulation of DNA damage.
Carotenuto, P; Amato, F; Lampis, A; Rae, C; Hedayat, S; et al. (NATURE PORTFOLIO, 2021-11-18)FOLFIRINOX, a combination of chemotherapy drugs (Fluorouracil, Oxaliplatin, Irinotecan -FOI), provides the best clinical benefit in pancreatic ductal adenocarcinoma (PDAC) patients. In this study we explore the role of ... -
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 ... -
Molecular profiling and combinatorial activity of CCT068127: a potent CDK2 and CDK9 inhibitor.
Whittaker, SR; Barlow, C; Martin, MP; Mancusi, C; Wagner, S; et al. (WILEY, 2018-03-01)Deregulation of the cyclin-dependent kinases (CDKs) has been implicated in the pathogenesis of multiple cancer types. Consequently, CDKs have garnered intense interest as therapeutic targets for the treatment of cancer. ... -
Native Size-Exclusion Chromatography-Based Mass Spectrometry Reveals New Components of the Early Heat Shock Protein 90 Inhibition Response Among Limited Global Changes.
Samant, RS; Batista, S; Larance, M; Ozer, B; Milton, CI; et al. (ELSEVIER, 2023-02-01)The molecular chaperone heat shock protein 90 (HSP90) works in concert with co-chaperones to stabilize its client proteins, which include multiple drivers of oncogenesis and malignant progression. Pharmacologic inhibitors ... -
Objective, Quantitative, Data-Driven Assessment of Chemical Probes.
Antolin, AA; Tym, JE; Komianou, A; Collins, I; Workman, P; et al. (CELL PRESS, 2018-02-15)Chemical probes are essential tools for understanding biological systems and for target validation, yet selecting probes for biomedical research is rarely based on objective assessment of all potential compounds. Here, we ... -
Oncogenic RAC1 and NRAS drive resistance to endoplasmic reticulum stress through MEK/ERK signalling.
Bright, MD; Clarke, PA; Workman, P; Davies, FE (ELSEVIER SCIENCE INC, 2018-04-01)Cancer cells are able to survive under conditions that cause endoplasmic reticulum stress (ER-stress), and can adapt to this stress by upregulating cell-survival signalling pathways and down-regulating apoptotic pathways. ...