| Compound Information | SONAR Target prediction |
| Name: | HYDROXYUREA |
| Unique Identifier: | SPE01500344 |
| MolClass: | Checkout models in ver1.5 and ver1.0 |
| Molecular Formula: | |
| Molecular Weight: | 72.023 g/mol |
| X log p: | -0.956 (online calculus) |
| Lipinksi Failures | 0 |
| TPSA | 17.07 |
| Hydrogen Bond Donor Count: | 0 |
| Hydrogen Bond Acceptors Count: | 2 |
| Rotatable Bond Count: | 1 |
| Canonical Smiles: | NC(=O)NO |
| Source: | synthetic |
| Therapeutics: | antineoplastic, inhibits ribonucleoside diphosphate reductase |
| Generic_name: | Hydroxyurea |
| Chemical_iupac_name: | hydroxyurea |
| Drug_type: | Approved Drug |
| Pharmgkb_id: | PA449942 |
| Kegg_compound_id: | C07044 |
| Drugbank_id: | APRD00023 |
| Melting_point: | 142-146 oC |
| H2o_solubility: | 1E+006 mg/L |
| Logp: | -1.432 |
| Cas_registry_number: | 07/01/127 |
| Drug_category: | Antisickling Agents; Antineoplastic Agents; ATC:L01A |
| Indication: | For management of melanoma, resistant chronic myelocytic leukemia, and recurrent, metastatic, or inoperable carcinoma of the ovary and Sickle-cell anemia. |
| Pharmacology: | Hydroxyurea has dose-dependent synergistic activity with cisplatin in vitro. In vivo 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. |
| Mechanism_of_action: | 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. |
| Organisms_affected: | Humans and other mammals |
| Found: 9 active | as graph: single | with analogs | 1 2 3 4 5 6 7 8 9 Next >> |
| Species: | 4932 |
| Condition: | SPE01500767 |
| Replicates: | 2 |
| Raw OD Value: r im | 0.6937±0 |
| Normalized OD Score: sc h | 0.9008±0 |
| Z-Score: | -4.0084±0 |
| p-Value: | 0.0000611382 |
| Z-Factor: | 0.349025 |
| Fitness Defect: | 9.7024 |
| Bioactivity Statement: | Active |
| ps |
| DBLink | Rows returned: 2 |
| 3657 | hydroxyurea |
| 450684 | hydroxyurea |
| internal high similarity DBLink | Rows returned: 1 |
| LOPAC 00959 | 1.0000 |
| active | Cluster 585 | Additional Members: 3 | Rows returned: 1 |
| LOPAC 00959 | 0 |
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