Repositioning Candidate Details
| Candidate ID: | R0096 |
| Source ID: | DB00261 |
| Source Type: | approved |
| Compound Type: | small molecule |
| Compound Name: | Anagrelide |
| Synonyms: | Anagrelide |
| Molecular Formula: | C10H7Cl2N3O |
| SMILES: | ClC1=CC=C2N=C3NC(=O)CN3CC2=C1Cl |
| Structure: |
|
| DrugBank Description: | Anagrelide is a platelet-reducing agent used to lower dangerously elevated platelet levels (i.e. to treat thrombocythemia) in patients with myeloproliferative neoplasms. It is an oral imidazoquinazoline that was first approved for use in the US in 1997. It appears to carry a better response rate than other thrombocythemia treatments (e.g. , ) and may be better tolerated. |
| CAS Number: | 68475-42-3 |
| Molecular Weight: | 256.088 |
| DrugBank Indication: | Anagrelide is indicated for the treatment of thrombocythemia, secondary to malignant neoplasms, to reduce platelet count and the associated risk of thrombosis. It is also beneficial in the amelioration of thrombocythemia symptoms including thrombo-hemorrhagic events. |
| DrugBank Pharmacology: | Anagrelide decreases platelet counts by suppressing transcription factors necessary for the synthesis and maturation of platelet-producing cells. The drug itself appears to have a relatively short residence time in the body necessitating twice or four times daily dosing. However, given that the pharmacological effect of anagrelide therapy is reliant on a gradual suppression of platelet-producing cells, it may take 7 to 14 days for its administration to be reflected in reduced platelet counts - for this reason any changes to anagrelide doses should not exceed 0.5 mg/day in any one week. Evidence from animal studies suggests anagrelide may impair female fertility. Female patients of reproductive age should be advised of the potential for adverse effects on fertility prior to initiating therapy. |
| DrugBank MoA: | The exact mechanism by which anagrelide lowers platelet count is unclear. Evidence from human trials suggests a dose-related suppression of megakaryocyte maturation, the cells responsible for platelet production - blood drawn from patients receiving anagrelide showed a disruption to the post-mitotic phase of megakaryocyte development and a subsequent reduction in their size and ploidy. This may be achieved via indirect suppression of certain transcription factors required for megakaryocytopoeisis, including GATA-1 and FOG-1. Anagrelide is a known inhibitor of phosphodiesterase 3A (PDE3A), although its platelet-lowering effects appear unrelated to this inhibition. While PDE3 inhibitors, as a class, can inhibit platelet aggregation, this effect is only seen at higher anagrelide doses (i.e. greater than those required to reduce platelet count). Modulation of PDE3A has been implicated in causing cell cycle arrest and apoptosis in cancer cells expressing both PDE3A and SLFN12, and may be of value in the treatment of gastrointestinal stromal tumours. |
| Targets: | cGMP-inhibited 3',5'-cyclic phosphodiesterase A inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|