1398230-14-2Relevant academic research and scientific papers
DEOXYCYTIDINE KINASE INHIBITORS
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, (2015/02/25)
Provided herein are compounds that bind to dCK and methods for treating cancer.
Development of new deoxycytidine kinase inhibitors and noninvasive in vivo evaluation using positron emission tomography
Murphy, Jennifer M.,Armijo, Amanda L.,Nomme, Julian,Lee, Chi Hang,Smith, Quentin A.,Li, Zheng,Campbell, Dean O.,Liao, Hsiang-I.,Nathanson, David A.,Austin, Wayne R.,Lee, Jason T.,Darvish, Ryan,Wei, Liu,Wang, Jue,Su, Ying,Damoiseaux, Robert,Sadeghi, Saman,Phelps, Michael E.,Herschman, Harvey R.,Czernin, Johannes,Alexandrova, Anastassia N.,Jung, Michael E.,Lavie, Arnon,Radu, Caius G.
, p. 6696 - 6708 (2013/10/01)
Combined inhibition of ribonucleotide reductase and deoxycytidine kinase (dCK) in multiple cancer cell lines depletes deoxycytidine triphosphate pools leading to DNA replication stress, cell cycle arrest, and apoptosis. Evidence implicating dCK in cancer cell proliferation and survival stimulated our interest in developing small molecule dCK inhibitors. Following a high throughput screen of a diverse chemical library, a structure-activity relationship study was carried out. Positron Emission Tomography (PET) using 18F-L-1-(2′-deoxy-2′-FluoroArabinofuranosyl) Cytosine (18F-L-FAC), a dCK-specific substrate, was used to rapidly rank lead compounds based on their ability to inhibit dCK activity in vivo. Evaluation of a subset of the most potent compounds in cell culture (IC50 = ～1-12 nM) using the 18F-L-FAC PET pharmacodynamic assay identified compounds demonstrating superior in vivo efficacy.
DEOXYCYTIDINE KINASE BINDING COMPOUNDS
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, (2012/09/22)
The invention provides compounds that bind to deoxycytidine kinase (dCK) and compositions including pharmaceutically acceptable compositions containing the compounds. The compounds are useful in treating diseases and disorders where dCK activity is implicated such as cancer and immune disorders. The compounds also find use in clinical methodologies including positron emission tomography (PET) imaging.
