Pyrimidine, also known as 1,3-diazobenzene, is a heterocyclic compound with the chemical formula C4H4N2. Pyrimidine is formed by substituting 2 nitrogen atoms for 2 carbons in the meta-position of benzene. It is a diazine and retains its aromaticity. Derivatives of pyrimidine widely exist in organic macromolecular nucleic acids, and many drugs also contain pyrimidine rings. In nucleic acids, three nucleobases are pyrimidine derivatives: cytosine, thymine and uracil. There are a variety of pyrimidine-containing drugs on the market, most of which are kinase inhibitors.
Epstein–Barr virus (EBV) has been associated with malignant lymphomas of B-cell, T-cell, and NK-cell origin. EBV infection of lymphoma cells leads to the development of cancers with an unmet medical need. The innovative ‘Kick and Kill’ approach targets EBV with Nanatinostat and Valganciclovir, in which Nanatinostat activates Ganciclovir by inducing the expression of EBV kinase genes. Ganciclovir then converts to cytotoxic form and results in apoptosis
Histone deacetylase (HDAC) is involved in the regulation of gene expression. HDAC inhibition induces cell cycle arrest and reactivates normal expression of tumor cells. Nanatinostat is such a potent hydroxamic acid-based class I-selective HDAC inhibitor. Nanatinostat is being studied with the antiviral agent Valganciclovir in EBV-associated malignancies. Viracta Therapeutics recently reports positive topline Nana-val results from stage 1 of the NAVAL-1 Trial from both arms of the relapsed or refractory (R/R) Epstein-Barr virus-positive (EBV+) peripheral T-cell lymphoma (PTCL) cohort.