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Tetrahydrouridine is a synthetic pyrimidine nucleoside analogue and a potent inhibitor of cytidine deaminase (CDA), an enzyme that catalyzes the deamination and inactivation of cytidine analogues. By inhibiting CDA, tetrahydrouridine prevents the breakdown of certain chemotherapeutic agents such as decitabine and gemcitabine, thereby enhancing their bioavailability and therapeutic efficacy. It is primarily used as an adjunct in cancer therapy to increase the effectiveness of these drugs by prolonging their action and improving tissue distribution. Additionally, tetrahydrouridine has been shown to inhibit cell proliferation through cell cycle regulation at the G1/S checkpoint independently of CDA inhibition. The drug has been investigated in clinical trials for various cancers including lung neoplasms, breast neoplasms, head and neck cancer as well as sickle cell disease[1][2][3][4][5][6][7][8].
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