Repositioning Candidate Details
| Candidate ID: | R1052 |
| Source ID: | DB06595 |
| Source Type: | approved; investigational |
| Compound Type: | small molecule |
| Compound Name: | Midostaurin |
| Synonyms: | 4'-N-benzoylstaurosporine; Midostaurin |
| Molecular Formula: | C35H30N4O4 |
| SMILES: | CO[C@@H]1[C@@H](C[C@H]2O[C@]1(C)N1C3=C(C=CC=C3)C3=C1C1=C(C4=C(C=CC=C4)N21)C1=C3CNC1=O)N(C)C(=O)C1=CC=CC=C1 |
| Structure: |
|
| DrugBank Description: | Midostaurin (as Rydapt) is a multitarget kinase inhibitor for the treatment for adult patients with newly diagnosed acute myeloid leukemia (AML) who have a specific genetic mutation called FLT3. It was initially characterized as a potential broad-spectrum antineoplastic agent, with activity toward diverse solid and hematopoietic tumors . It was approved on April 28, 2017 and has shown to increase the overall survival rate in patients with AML as an adjunct therapy along with chemotherapeutic agents. |
| CAS Number: | 120685-11-2 |
| Molecular Weight: | 570.649 |
| DrugBank Indication: | Investigated for use/treatment in adult patients with high-risk acute myeloid leukemia (AML) who are FLT3 mutation-positive, agressive systemic mastocytosis (ASM), systemic mastocytosis with associated hematological neoplasm (SM-AHN), or mast cell leukemia (MCL). |
| DrugBank Pharmacology: | It targets multiple WT and mutated kinases that, when activated, constitutively stimulate aberrant signalling cascades that lead to malignancies such as AML and ASM. Alternative pharmacodynamic effect of midostaurin in prolonging QTc intervals was not clinically significant in patients with advanced SM or AML when compared to placebo. Midostaurin is therapeutically beneficial as a combination therapy for patients undergoing chemotherapy. |
| DrugBank MoA: | It potently inhibits multiple receptor tyrosine kinases. Midostaurin and its major active metabolites CGP62221 and CGP52421 inhibit the activity of protein kinase C alpha (PKCalpha), VEGFR2, KIT, PDGFR and WT and/or mutant FLT3 tyrosine kinases. Inhibition of FLT3 receptor signalling cascades induces apoptosis of target leukemia cells expressing target receptors and mast cells, in addition to its antiproliferative activity toward multiple cancer cell lines . Midostaurin also interacts with organic anion transporter (OATP) 1A1 and multidrug resistance protein (MRP)-2 according to preliminary in vitro studies. |
| Targets: | Protein kinase C alpha type antagonist&inhibitor; Vascular endothelial growth factor receptor 2 antagonist&inhibitor; Mast/stem cell growth factor receptor Kit antagonist&inhibitor; Platelet-derived growth factor receptor alpha antagonist&inhibitor; Platelet-derived growth factor receptor beta antagonist&inhibitor; Receptor-type tyrosine-protein kinase FLT3 antagonist&inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
| Diseases ID | DO ID | Disease Name | Definition | Class |
|---|