Comprehensive Monograph on Hydroxyurea (DB01005)

Section 1: Overview and Key Findings

[Hydroxyurea (also known as hydroxycarbamide) is a small molecule antimetabolite with a remarkable and enduring legacy in modern medicine. First synthesized in 1869 and receiving its initial U.S. Food and Drug Administration (FDA) approval in 1967, this agent possesses a distinct dual therapeutic identity.][1][ On one hand, it functions as a potent cytotoxic drug, indicated for the treatment of certain myeloproliferative neoplasms and as a radiosensitizing agent in head and neck cancers.][4][ This activity is driven by its foundational mechanism: the inhibition of ribonucleotide reductase, an enzyme essential for DNA synthesis and cellular proliferation.][1]

[On the other hand, through a distinct pharmacological pathway discovered decades after its initial approval, Hydroxyurea has become the cornerstone disease-modifying therapy for sickle cell disease (SCD).][2][ Its efficacy in this genetic hemoglobinopathy stems from its ability to induce the production of fetal hemoglobin (HbF), which interferes with the pathological polymerization of sickle hemoglobin (HbS), thereby ameliorating the primary driver of the disease.][1][ The clinical journey of Hydroxyurea exemplifies the profound impact of drug repurposing, where deeper pharmacological investigation has unlocked novel therapeutic potential in a well-established molecule.]