decitabine + tetrahydrouridine

Decitabine + tetrahydrouridine is an oral fixed-dose combination of two small molecules developed for the treatment of sickle cell disease and other hemoglobinopathies. Decitabine is a deoxycytidine analog that inhibits DNA methyltransferase 1 (DNMT1), leading to hypomethylation of DNA and reactivation of silenced genes such as those responsible for fetal hemoglobin production. Tetrahydrouridine acts as a competitive inhibitor of cytidine deaminase (CDA), an enzyme that rapidly inactivates decitabine; by inhibiting CDA, tetrahydrouridine increases the bioavailability and half-life of decitabine when administered orally. This combination allows for non-cytotoxic epigenetic gene regulation, specifically increasing fetal hemoglobin levels to ameliorate symptoms in sickle cell disease patients[2][3][5][6][7]. The drug is being developed by EpiDestiny (now part of Novo Nordisk) and has been evaluated in clinical trials for safety, pharmacokinetics, pharmacodynamics, and efficacy in inducing fetal hemoglobin[2][3].

Other names

NDecTHU–decitabineTHU-DAC