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Small-molecule targeting of brachyury transcription factor addiction in chordoma.
(2019-02)
Chordoma is a primary bone cancer with no approved therapy 1 . The identification of therapeutic targets in this disease has been challenging due to the infrequent occurrence of clinically actionable somatic mutations in ...
Structure-Based Optimization of Potent, Selective, and Orally Bioavailable CDK8 Inhibitors Discovered by High-Throughput Screening.
(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 ...
Discovery of potent, orally bioavailable, small-molecule inhibitors of WNT signaling from a cell-based pathway screen.
(AMER CHEMICAL SOC, 2015-02-26)
WNT signaling is frequently deregulated in malignancy, particularly in colon cancer, and plays a key role in the generation and maintenance of cancer stem cells. We report the discovery and optimization of a 3,4,5-trisubstituted ...
Overexpression of EZH2 in multiple myeloma is associated with poor prognosis and dysregulation of cell cycle control.
(SPRINGERNATURE, 2017-03-31)
Myeloma is heterogeneous at the molecular level with subgroups of patients characterised by features of epigenetic dysregulation. Outcomes for myeloma patients have improved over the past few decades except for molecularly ...
Inhibitors of cyclin-dependent kinases as cancer therapeutics.
(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 ...
CHK1 Inhibition Is Synthetically Lethal with Loss of B-Family DNA Polymerase Function in Human Lung and Colorectal Cancer Cells.
(AMER ASSOC CANCER RESEARCH, 2020-04-15)
Checkpoint kinase 1 (CHK1) is a key mediator of the DNA damage response that regulates cell-cycle progression, DNA damage repair, and DNA replication. Small-molecule CHK1 inhibitors sensitize cancer cells to genotoxic ...
Molecular profiling and combinatorial activity of CCT068127: a potent CDK2 and CDK9 inhibitor.
(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. ...