Repositioning Candidate Details
| Candidate ID: | R1447 |
| Source ID: | DB12442 |
| Source Type: | investigational |
| Compound Type: | small molecule |
| Compound Name: | Alvespimycin |
| Synonyms: | 17-(dimethylaminoethylamino)-17-demethoxygeldanamycin; 17-DMAG; Alvespimycin; DMAG |
| Molecular Formula: | C32H48N4O8 |
| SMILES: | CO[C@H]1C[C@H](C)CC2=C(NCCN(C)C)C(=O)C=C(NC(=O)\C(C)=C\C=C/[C@H](OC)[C@@H](OC(N)=O)\C(C)=C\[C@H](C)[C@H]1O)C2=O |
| Structure: |
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| DrugBank Description: | Alvespimycin is a derivative of geldanamycin and heat shock protein (HSP) 90 inhibitor. It has been used in trials studying the treatment of solid tumor in various cancer as an antitumor agent. In comparison to the first HSP90 inhibitor tanespimycin, it exhibits some pharmacologically desirable properties such as reduced metabolic liability, lower plasma protein binding, increased water solubility, higher oral bioavailability, reduced hepatotoxicity and superior antitumor activity . |
| CAS Number: | 467214-20-6 |
| Molecular Weight: | 616.7455 |
| DrugBank Indication: | Investigated for use as an antineoplastic agent for solid tumors, advanced solid tumours or acute myeloid leukaemia. |
| DrugBank Pharmacology: | Alvespimycin mediates an antitumor activity through HSP90 inhibition that targets client proteins for proteasomal destruction, including oncogenic kinases such as BRAF. The administration of the drug is shown to result in the depletion of client proteins that have oncogenic activity and potential induction of HSP70 (HSP72) . It is more selective for tumors over normal tissue. A study also reports that alvespimycin enhances the potency of telomerase inhibition by imetelstat in pre-clinical models of human osteosarcoma . |
| DrugBank MoA: | Alvespimycin inhibits HSP90 and its regulation of correct folding and function of many cellular signalling proteins, which are referred to as Hsp90 client proteins. These client proteins are also referred to as oncoproteins and include Her-2, EGFR, Akt, Raf-1, p53, Bcr-Abl, Cdk4, Cdk6 and steroid receptors that are involved in cellular signalling pathways that drive cellular proliferation and counteract apoptosis. They are often over-expressed or mutated in tumors, and contribute to cancer progression and therapy resistance . Alvespimycin promotes an anticancer activity by disrupting Hsp90's chaperone function and inducing the proteasomal degradation of oncoproteins. It is shown to reduce the levels of CDK4 and ERBB2 . |
| Targets: | Heat shock protein HSP 90-alpha inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
