Repositioning Candidate Details
| Candidate ID: | R0299 |
| Source ID: | DB01005 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Hydroxyurea |
| Synonyms: | |
| Molecular Formula: | CH4N2O2 |
| SMILES: | NC(=O)NO |
| Structure: |
|
| DrugBank Description: | An antineoplastic agent that inhibits DNA synthesis through the inhibition of ribonucleoside diphosphate reductase. |
| CAS Number: | 127-07-1 |
| Molecular Weight: | 76.0547 |
| DrugBank Indication: | For management of melanoma, resistant chronic myelocytic leukemia, and recurrent, metastatic, or inoperable carcinoma of the ovary and Sickle-cell anemia. |
| DrugBank Pharmacology: | Hydroxyurea has dose-dependent synergistic activity with cisplatin <i>in vitro</i>. <i>In vivo</i> Hydroxyurea showed activity in combination with cisplatin against the LX-1 and CALU-6 human lung xenografts, but minimal activity was seen with the NCI-H460 or NCI-H520 xenografts. Hydroxyurea was synergistic with cisplatin in the Lewis lung murine xenograft. Sequential exposure to Hydroxyurea 4 hours before cisplatin produced the greatest interaction. |
| DrugBank MoA: | Hydroxyurea is converted to a free radical nitroxide (NO) in vivo, and transported by diffusion into cells where it quenches the tyrosyl free radical at the active site of the M2 protein subunit of ribonucleotide reductase, inactivating the enzyme. The entire replicase complex, including ribonucleotide reductase, is inactivated and DNA synthesis is selectively inhibited, producing cell death in S phase and synchronization of the fraction of cells that survive. Repair of DNA damaged by chemicals or irradiation is also inhibited by hydroxyurea, offering potential synergy between hydroxyurea and radiation or alkylating agents. Hydroxyurea also increases the level of fetal hemoglobin, leading to a reduction in the incidence of vasoocclusive crises in sickle cell anemia. Levels of fetal hemoglobin increase in response to activation of soluble guanylyl cyclase (sGC) by hydroxyurea-derived NO. |
| Targets: | Ribonucleoside-diphosphate reductase large subunit |
| Inclusion Criteria: |
| Strategy ID | Strategy | Synonyms | Related Targets | Related Drugs |
|---|
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|