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Publications

ATR inhibition facilitates targeting of leukemia dependence on convergent nucleotide biosynthetic pathways

1st September 2017/in Publications /by admin

Abstract Leukemia cells rely on two nucleotide biosynthetic pathways, de novo and salvage, to produce dNTPs for DNA replication. Here, using metabolomic, proteomic, and phosphoproteomic approaches, we show that inhibition of the replication stress sensing kinase ataxia telangiectasia and Rad3-related protein (ATR) reduces the output of both de novo and salvage pathways by regulating the […]

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Structure-Guided Development of Deoxycytidine Kinase Inhibitors with Nanomolar Affinity and Improved Metabolic Stability

26th November 2014/in Publications /by admin

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 […]

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http://trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png 0 0 admin http://trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png admin2014-11-26 12:07:382017-03-06 12:10:05Structure-Guided Development of Deoxycytidine Kinase Inhibitors with Nanomolar Affinity and Improved Metabolic Stability

Deoxycytidine Kinase Augments ATM-Mediated DNA Repair and Contributes to Radiation Resistance

7th August 2014/in Publications /by admin

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 […]

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http://trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png 0 0 admin http://trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png admin2014-08-07 12:10:262017-03-06 12:11:07Deoxycytidine Kinase Augments ATM-Mediated DNA Repair and Contributes to Radiation Resistance

Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication

24th February 2014/in Publications /by admin

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. […]

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http://trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png 0 0 admin http://trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png admin2014-02-24 12:11:232017-03-06 12:12:06Co-targeting of convergent nucleotide biosynthetic pathways for leukemia eradication

Structural characterization of new deoxycytidine kinase inhibitors rationalizes the affinity-determining moieties of the molecules

1st January 2014/in Publications /by admin

Abstract: Deoxycytidine kinase (dCK) is a key enzyme in the nucleoside salvage pathway that is also required for the activation of several anticancer and antiviral nucleoside analog prodrugs. Additionally, dCK has been implicated in immune disorders and has been found to be overexpressed in several cancers. To allow the probing and modulation of dCK activity, […]

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http://trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png 0 0 admin http://trethera.com/wp-content/uploads/2015/12/trethera_logo-wo.png admin2014-01-01 12:12:162017-03-06 12:12:57Structural characterization of new deoxycytidine kinase inhibitors rationalizes the affinity-determining moieties of the molecules
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