5-fluoro-2'-deoxycytidine + tetrahydrouridine

5-fluoro-2'-deoxycytidine + tetrahydrouridine is a combination of two small molecules used in investigational cancer therapy. 5-fluoro-2'-deoxycytidine (FdCyd) is a nucleoside analog that acts as an inhibitor of DNA methyltransferase (DNMT), leading to hypomethylation of DNA and potential reactivation of tumor suppressor genes. Tetrahydrouridine (THU) is a potent inhibitor of cytidine deaminase, an enzyme that rapidly metabolizes FdCyd into inactive or toxic metabolites. By co-administering THU with FdCyd, the plasma concentration and half-life of FdCyd are increased, allowing for effective DNMT inhibition in vivo[1][2][6]. This combination has been evaluated in phase I and II clinical trials for advanced solid tumors including breast cancer, non-small cell lung cancer (NSCLC), head & neck cancers, urothelial carcinoma[1][3], and has also been studied preclinically in pediatric brain tumors[4]. While the regimen shows pharmacodynamic evidence of target engagement—such as increased p16 expression in circulating tumor cells—clinical efficacy has been limited except for some signals in urothelial carcinoma[1]. The drug pair is not approved for any indication.

Other names

FdCyd + THU5FD + THUFdCyd and tetrahydrouridine