Abstract: Brain-infiltrating leukocytes contribute to multiple sclerosis (MS) and autoimmune encephalomyelitis and likely play a role in traumatic brain injury, seizure, and stroke. Brain-infiltrating leukocytes are also primary targets for MS disease-modifying therapies. However, no method exists for noninvasively visualizing these cells in a living organism. 1-(2′-deoxy-2′-18F-fluoroarabinofuranosyl) cytosine (18F-FAC) is a PET radiotracer that measures […]
https://www.trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png00Trethera Supporthttps://www.trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.pngTrethera Support2021-03-05 03:57:462021-03-08 17:48:3418 F-FAC PET Visualizes Brain-Infiltrating Leukocytes in a Mouse Model of Multiple Sclerosis
Abstract: Recently, we have shown that small molecule dCK inhibitors in combination with pharmacological perturbations of de novo dNTP biosynthetic pathways could eliminate acute lymphoblastic leukemia cells in animal models. However, our previous lead compound had a short half-life in vivo. Therefore, we set out to develop dCK inhibitors with favorable pharmacokinetic properties. We delineated […]
https://www.trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png00adminhttps://www.trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.pngadmin2014-11-26 12:07:382017-03-06 12:10:05Structure-Guided Development of Deoxycytidine Kinase Inhibitors with Nanomolar Affinity and Improved Metabolic Stability
Abstract: Efficient and adequate generation of deoxyribonucleotides is critical to successful DNA repair. We show that ataxia telangiectasia mutated (ATM) integrates the DNA damage response with DNA metabolism by regulating the salvage of deoxyribonucleosides. Specifically, ATM phosphorylates and activates deoxycytidine kinase (dCK) at serine 74 in response to ionizing radiation (IR). Activation of dCK shifts […]
https://www.trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png00adminhttps://www.trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.pngadmin2014-08-07 12:10:262017-03-06 12:11:07Deoxycytidine Kinase Augments ATM-Mediated DNA Repair and Contributes to Radiation Resistance
Abstract: Pharmacological targeting of metabolic processes in cancer must overcome redundancy in biosynthetic pathways. Deoxycytidine (dC) triphosphate (dCTP) can be produced both by the de novo pathway (DNP) and by the nucleoside salvage pathway (NSP). However, the role of the NSP in dCTP production and DNA synthesis in cancer cells is currently not well understood. […]
Abstract: 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 […]
https://www.trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png00adminhttps://www.trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.pngadmin2013-09-12 12:13:062017-03-06 12:13:36Development of new deoxycytidine kinase inhibitors and non-invasive in vivo evaluation using Positron Emission Tomography
18 F-FAC PET Visualizes Brain-Infiltrating Leukocytes in a Mouse Model of Multiple Sclerosis
/in Publications /by Trethera SupportAbstract: Brain-infiltrating leukocytes contribute to multiple sclerosis (MS) and autoimmune encephalomyelitis and likely play a role in traumatic brain injury, seizure, and stroke. Brain-infiltrating leukocytes are also primary targets for MS disease-modifying therapies. However, no method exists for noninvasively visualizing these cells in a living organism. 1-(2′-deoxy-2′-18F-fluoroarabinofuranosyl) cytosine (18F-FAC) is a PET radiotracer that measures […]
Structure-Guided Development of Deoxycytidine Kinase Inhibitors with Nanomolar Affinity and Improved Metabolic Stability
/in Publications /by adminAbstract: Recently, we have shown that small molecule dCK inhibitors in combination with pharmacological perturbations of de novo dNTP biosynthetic pathways could eliminate acute lymphoblastic leukemia cells in animal models. However, our previous lead compound had a short half-life in vivo. Therefore, we set out to develop dCK inhibitors with favorable pharmacokinetic properties. We delineated […]
Deoxycytidine Kinase Augments ATM-Mediated DNA Repair and Contributes to Radiation Resistance
/in Publications /by adminAbstract: Efficient and adequate generation of deoxyribonucleotides is critical to successful DNA repair. We show that ataxia telangiectasia mutated (ATM) integrates the DNA damage response with DNA metabolism by regulating the salvage of deoxyribonucleosides. Specifically, ATM phosphorylates and activates deoxycytidine kinase (dCK) at serine 74 in response to ionizing radiation (IR). Activation of dCK shifts […]
Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication
/in Publications /by adminAbstract: Pharmacological targeting of metabolic processes in cancer must overcome redundancy in biosynthetic pathways. Deoxycytidine (dC) triphosphate (dCTP) can be produced both by the de novo pathway (DNP) and by the nucleoside salvage pathway (NSP). However, the role of the NSP in dCTP production and DNA synthesis in cancer cells is currently not well understood. […]
Development of new deoxycytidine kinase inhibitors and non-invasive in vivo evaluation using Positron Emission Tomography
/in Publications /by adminAbstract: 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 […]