Industrial policy-making after COVID-19: manufacturing, innovation and sustainability
Date
2021
Authors
Dean, M.
Rainnie, A.
Stanford, J.
Nahum, D.
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Journal article
Citation
Economic and Labour Relations Review, 2021; 32(2):283-303
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Abstract
CDK8 regulates transcription either by phosphorylation of transcription factors or, as part of a four-subunit kinase module, through a reversible association of the kinase module with the Mediator complex, a highly conserved transcriptional coactivator. Deregulation of CDK8 has been found in various types of human cancer, while the role of CDK8 in supressing anti-cancer response of natural killer cells is being understood. Currently, CDK8-targeting cancer drugs are highly sought-after. Herein we detail the discovery of a series of novel pyridine-derived CDK8 inhibitors. Medicinal chemistry optimisation gave rise to 38 (AU1-100), a potent CDK8 inhibitor with oral bioavailability. The compound inhibited the proliferation of MV4-11 acute myeloid leukaemia cells with the kinase activity of cellular CDK8 dampened. No systemic toxicology was observed in the mice treated with 38. These results warrant further pre-clinical studies of 38 as an anti-cancer agent.
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Data source: Supplementary data, https://doi.org/10.1016/j.ejmech.2021.113248
Link to a related website: https://journals.sagepub.com/doi/pdf/10.1177/10353046211014755, Open Access via Unpaywall
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Copyright 2021 The Author(s) 2021