Abstract: Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

Abstract: Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

Abstract: Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions in a method of treating cancer. The dUTPase inhibitors disclosed contain a uracil isostere in the molecule represented by a 2,6-diketopiperazine moiety. Thioanalogs of the uracil isostere where a thione replaces each of the ketone are also disclosed.

Abstract: Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

Abstract: Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions in a method of treating cancer. The dUTPase inhibitors disclosed contain a uracil isostere in the molecule represented by a 2,6-diketopiperazine moiety. Thioanalogs of the uracil isostere where a thione replaces each of the ketone are also disclosed.

Abstract: Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions in a method of treating cancer. The dUTPase inhibitors disclosed contain a uracil isostere in the molecule represented by a 2,6-diketopiperazine moiety. Thioanalogs of the uracil isostere where a thione replaces each of the ketone are also disclosed.

Abstract: Provided herein are dUTPase inhibitors, compositions comprising such compounds and methods of using such compounds and compositions.

Abstract: The inventors have developed a rapid and sensitive fluorescence-based assay to quantify dNTPs. This assay relies on the principle that incorporation of a limiting dNTP is required for primer-extension and polymerase-mediated 5-3? exonuclease hydrolysis of a quenched fluorophore-labeled probe resulting in fluorescence. The concentration of limiting dNTPs is directly proportional to the fluorescence generated. This assay has important applications in research that investigates the influence of pathological conditions or pharmacological agents on dNTP biosynthesis and regulation.

Abstract: The inventors have developed a rapid and sensitive fluorescence-based assay to quantify dNTPs. This assay relies on the principle that incorporation of a limiting dNTP is required for primer-extension and polymerase-mediated 5-3? exonuclease hydrolysis of a quenched fluorophore-labeled probe resulting in fluorescence. The concentration of limiting dNTPs is directly proportional to the fluorescence generated. This assay has important applications in research that investigates the influence of pathological conditions or pharmacological agents on dNTP biosynthesis and regulation.

Abstract: Evidence demonstrating that elevated expression of dUTPase protects breast cancer cells from the expansion of the intracellular uracil pool, translating to reduced growth inhibition following treatment with 5-FU is provided. The implementation of in silica drug development techniques to identify and develop small molecule inhibitors of dUTPase are reported. As 5-FU and the oral 5-FU pro-drug capecitabine remain central agents in the treatment of a variety of malignancies, the clinical utility of a small molecule inhibitor to dUTPase represents a viable strategy to improve the clinical efficacy of these mainstay chemotherapeutic agents.

Abstract: A screening and development of agents that target and disrupt DNA replication is provided. In particular, aberrant UT1 metabolism is provided as a mechanism of inducing cytotoxicity and/or cytostasis.

Abstract: The invention provides the DNA and amino acid sequence of dUTPase, an enzyme which is essential for life and which is increased during periods of cellular proliferation. The human form of the dUTPase enzyme has been found to have two isoforms, a nuclear and a mitochondrial isoform. Methods of determining the proliferation status of a cell, efficacy of antineoplastic compounds, and response to therapy with antineoplastic compounds, using cellular levels of dUTPase is disclosed. A kit containing the necessary reagents for the determination of dUTPase is also disclosed.