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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 ...
Assessing the mechanism and therapeutic potential of modulators of the human Mediator complex-associated protein kinases.
(ELIFE SCIENCES PUBLICATIONS LTD, 2016-12-09)
Mediator-associated kinases CDK8/19 are context-dependent drivers or suppressors of tumorigenesis. Their inhibition is predicted to have pleiotropic effects, but it is unclear whether this will impact on the clinical utility ...
Inhibition of mTOR-kinase destabilizes MYCN and is a potential therapy for MYCN-dependent tumors.
(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 ...
A selective chemical probe for exploring the role of CDK8 and CDK19 in human disease.
(NATURE PUBLISHING GROUP, 2015-12-01)
There is unmet need for chemical tools to explore the role of the Mediator complex in human pathologies ranging from cancer to cardiovascular disease. Here we determine that CCT251545, a small-molecule inhibitor of the WNT ...
Loss of heterozygosity as a marker of homologous repair deficiency in multiple myeloma: a role for PARP inhibition?
(NATURE PUBLISHING GROUP, 2018-07-01)
PARP inhibitors can induce synthetic lethality in tumors characterized by homologous recombination deficiency (HRD), which can be detected by evaluating genome-wide loss of heterozygosity (LOH). Multiple myeloma (MM) is a ...
The genomic landscape of plasma cells in systemic light chain amyloidosis.
(AMER SOC HEMATOLOGY, 2018-12-27)
Noncoding RNA in Cholangiocarcinoma.
(THIEME MEDICAL PUBL INC, 2019-02-01)
Cholangiocarcinomas (CCAs) are tumors with a dismal prognosis. Early diagnosis is a key challenge because of the lack of specific symptoms, and the curability rate is low due to the difficulty in achieving a radical resection ...
Toward personalized treatment in multiple myeloma based on molecular characteristics.
(AMER SOC HEMATOLOGY, 2019-02-14)
To date, the choice of therapy for an individual multiple myeloma patient has been based on clinical factors such as age and comorbidities. The widespread evolution, validation, and clinical utilization of molecular ...
canSAR: update to the cancer translational research and drug discovery knowledgebase.
(OXFORD UNIV PRESS, 2019-01-08)
canSAR (http://cansar.icr.ac.uk) is a public, freely available, integrative translational research and drug discovery knowlegebase. canSAR informs researchers to help solve key bottlenecks in cancer translation and drug ...