Hydroxyurea

Hydroxyurea is changed in the body into a free radical nitroxide, called NO. It moves by diffusion into cells, where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, which switches the enzyme off. The whole replicase complex, ribonucleotide reductase included, is shut down, and DNA synthesis is selectively blocked. This kills cells in the S phase and brings the cells that survive into step with one another. Hydroxyurea also stops the repair of DNA damaged by chemicals or radiation, which is why it may work well alongside radiation or alkylating agents. Hydroxyurea also raises the level of fetal hemoglobin. In sickle cell anemia this means fewer vasoocclusive crises. The rise in fetal hemoglobin happens because the NO produced from hydroxyurea activates soluble guanylyl cyclase (sGC).