Toby Roe

Inhibition of cyclin-dependent kinase 8 modulates chondrocyte transition to hypertrophy and provides in vivo protection against spontaneous osteoarthritis

Leah M. Wells, Jacob A. C. Keen, Aikta Sharma, Neil Marr et autres

Chondrocyte hypertrophy is a key hallmark of osteoarthritis (OA) that drives a multitude of whole-joint disease processes. There are no approved disease-modifying pharmaceuticals in clinical use, emphasising the urgent need for innovative therapeutics. Screening of a focussed chemical library using a novel …

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Abstract 6005: Human DEAH-box RNA helicase 8 regulates HSF1-mediated stress response and cancer-associated pre-mRNA splicing.

Jennifer R. Tall, Robert te Poele, Alexandra Iulia Vasile, Pradeep Ramagiri et autres

Abstract Background: Heat Shock Factor 1 (HSF1) drives stress tolerance, oncogenic transformation, and survival in diverse human cancers. Although pharmacologic inhibition of HSF1 remains challenging, identifying druggable upstream regulators of HSF1 offers a promising alternative strategy to disrupt stress adaptation in tumours. …

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Human DEAH-box helicase 8 regulates HSF1-mediated stress response and cancer-associated pre-mRNA splicing in tumour cells

Jennifer R. Tall, Robert te Poele, Alexandra Iulia Vasile, Pradeep Ramagiri et autres

Abstract Transcription factor heat shock factor 1 (HSF1) orchestrates the cellular stress response, promoting malignant transformation, unchecked proliferation, and stress-resilient survival of tumour cells. We set out to discover potentially druggable regulators of HSF1 activation and identified DEAH-box RNA helicase 8 (DHX8). …

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Mediator Kinase Inhibitor Selectivity and Activity in Colorectal Cancer

María Jesús Ortiz-Ruiz, Olajumoke Adeniji-Popoola, Konstantinos Mitsopoulos, Robert te Poele et autres

High Resolution Image Download MS PowerPoint Slide The Mediator complex is a regulator of gene expression, influencing chromatin structure and RNA polymerase II-mediated transcription. Its activity is controlled by a protein kinase module, which includes cyclin-dependent kinases 8 and 19, that phosphorylates …

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Abstract 524: Using acquired resistance to explore the mechanism of action of the integrated stress response/GCN2 activator NXP800 - A new developmental agent for platinum-resistant ARID1A mutant ovarian cancer

Marissa V. Powers, Rachel E. Hodgson, Swee Y. Sharp, Toby Roe et autres

Abstract Background: NXP800 is a potent, oral activator of the Integrated Stress response (ISR), inhibitor of heat shock factor 1 (HSF1) activation and tumor cell proliferation, which is in early clinical studies in ARID1A-mutated, platinum resistant, clear cell ovarian cancer (NCT05226507). We …

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Abstract PR-002: Activation of the integrated stress response by NXP800, an orally available, clinical-stage, investigational agent in ARID1A-mutated, platinum resistant ovarian cancer

Marissa V. Powers, Swee Y. Swap, Robert te Poele, Eirini-Maria Lampraki et autres

Abstract Using innovative phenotypic screening, targeting the Heat Shock Factor 1 (HSF1) pathway, followed by multiparameter medicinal chemistry optimization, we discovered NXP800, an orally active, potent inhibitor of cell proliferation. Evaluation in a mini-panel of human cancer cell lines and tumor xenografts …

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Abstract LB234: Activation of the integrated stress response by the developmental HSF1 pathway inhibitor NXP800

Marissa V. Powers, Swee Y. Sharp, Eirini-Maria Lampraki, Toby Roe et autres

Abstract HSF1 is a stress-inducible transcription factor that regulates the eukaryotic heat shock response (HSR). HSF1 activation induces the expression of multiple proteins needed for cellular recovery from stress. HSF1 also plays a key role in tumorigenesis and regulates the expression of …

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Supplementary Tables 2 and 3 from A Gene Expression Signature Associated with Metastatic Outcome in Human Leiomyosarcomas

Yin-Fai Lee, Megan John, Alison Falconer, S.A. Edwards et autres

Supplementary Tables 2 and 3 from A Gene Expression Signature Associated with Metastatic Outcome in Human Leiomyosarcomas

Supplementary Figure 1 from A Gene Expression Signature Associated with Metastatic Outcome in Human Leiomyosarcomas

Yin-Fai Lee, Megan John, Alison Falconer, S.A. Edwards et autres

Supplementary Figure 1 from A Gene Expression Signature Associated with Metastatic Outcome in Human Leiomyosarcomas

Supplementary Table 1 from A Gene Expression Signature Associated with Metastatic Outcome in Human Leiomyosarcomas

Yin-Fai Lee, Megan John, Alison Falconer, S.A. Edwards et autres

Supplementary Table 1 from A Gene Expression Signature Associated with Metastatic Outcome in Human Leiomyosarcomas

Data from A Gene Expression Signature Associated with Metastatic Outcome in Human Leiomyosarcomas

Yin-Fai Lee, Megan John, Alison Falconer, S.A. Edwards et autres

Abstract Metastasis is a major factor associated with poor prognosis in cancer, but little is known of its molecular mechanisms. Although the clinical behavior of soft tissue sarcomas is highly variable, few reliable determinants of outcome have been identified. New markers that …

Data from A Gene Expression Signature Associated with Metastatic Outcome in Human Leiomyosarcomas

Yin-Fai Lee, Megan John, Alison Falconer, S.A. Edwards et autres

Abstract Metastasis is a major factor associated with poor prognosis in cancer, but little is known of its molecular mechanisms. Although the clinical behavior of soft tissue sarcomas is highly variable, few reliable determinants of outcome have been identified. New markers that …