Repositioning Candidate Details
| Candidate ID: | R0268 |
| Source ID: | DB00928 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Azacitidine |
| Synonyms: | |
| Molecular Formula: | C8H12N4O5 |
| SMILES: | NC1=NC(=O)N(C=N1)[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O |
| Structure: |
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| DrugBank Description: | A pyrimidine nucleoside analogue that inhibits DNA methyltransferase, impairing DNA methylation. It is also an antimetabolite of cytidine, incorporated primarily into RNA. Azacytidine has been used as an antineoplastic agent. |
| CAS Number: | 320-67-2 |
| Molecular Weight: | 244.2047 |
| DrugBank Indication: | For treatment of patients with the following French-American-British myelodysplastic syndrome subtypes: refractory anemia or refractory anemia with ringed sideroblasts (if accompanied by neutropenia or thrombocytopenia or requiring transfusions), refractory anemia with excess blasts, refractory anemia with excess blasts in transformation (now classified as acute myelogenous leukemia with multilineage dysplasia), and chronic myelomonocytic leukemia. |
| DrugBank Pharmacology: | Azacitidine is believed to exert its antineoplastic effects by causing hypomethylation of DNA and direct cytotoxicity on abnormal hematopoietic cells in the bone marrow. The concentration of azacitidine required for maximum inhibition of DNA methylation in vitro does not cause major suppression of DNA synthesis. Hypomethylation may restore normal function to genes that are critical for differentiation and proliferation. The cytotoxic effects of azacitidine cause the death of rapidly dividing cells, including cancer cells that are no longer responsive to normal growth control mechanisms. Non-proliferating cells are relatively insensitive to azacitidine. Upon uptake into cells, azacitidine is phosphorylated to 5-azacytidine monophosphate by uridine-cytidine kinase, then to diphosphate by pyrimidine monophosphate kinases and triphosphate by diphosphate kinases. 5-Azacitidine triphosphate is incorporated into RNA, leading to the disruption of nuclear and cytoplasmic RNA metabolism and inhibition of protein synthesis. 5-Azacytidine diphosphate is reduced to 5-aza-deoxycytidine diphosphate by ribonucleotide reductase. The resultant metabolite is phosphorylated to 5-azadeoxycitidine triphosphate by nucleoside diphosphate kinases. 5-azadeoxycitidine triphosphate is then incoporated into DNA, leading to inhibition of DNA synthesis. Azacitidine is most toxic during the S-phase of the cell cycle. |
| DrugBank MoA: | Azacitidine (5-azacytidine) is a chemical analogue of the cytosine nucleoside used in DNA and RNA. Azacitidine may induce antineoplastic activity by inhibition of DNA methyltransferase at low doses and cytotoxicity through incorporation into RNA and DNA at high doses. Covalent binding to DNA methyltransferase results in hypomethylation of DNA and prevents DNA synthesis. As azacitidine is a ribonucleoside, it incoporates into RNA to a larger extent than into DNA. The incorporation into RNA leads to the dissembly of polyribosomes, defective methylation and acceptor function of transfer RNA, and inhibition of the production of protein, resulting in cell death. |
| Targets: | DNA (cytosine-5)-methyltransferase 1; RNA; DNA |
| Inclusion Criteria: |
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