Repositioning Candidate Details
| Candidate ID: | R1548 |
| Source ID: | DB14962 |
| Source Type: | approved; investigational |
| Compound Type: | biotech |
| Compound Name: | Trastuzumab deruxtecan |
| Synonyms: | fam-trastuzumab deruxtecan-nxki; Trastuzumab deruxtecan |
| Molecular Formula: | -- |
| SMILES: | -- |
| DrugBank Description: | Trastuzumab deruxtecan is a HER-2 directed antibody attached to a topoisomerase inhibitor that is approved for use in certain types of metastatic, unresectable breast cancer. It is classified as an antibody-drug conjugate. The cleavable peptide linker used to bind the antibody and drug in this product distinguishes it from other members of its class. Trastuzumab deruxtecan has been granted FDA approval for specific patients with HER-2 positive breast cancer who have failed other treatments. Promising results from a clinical trial prompted accelerated FDA approval for this indication on December 20, 2019. Trastuzumab deruxtecan was developed by Daiichi Sankyo in collaboration with AstraZeneca. The continued approval of this drug will depend on the confirmation of its beneficial effects in ongoing clinical trials. |
| CAS Number: | 1826843-81-5 |
| Molecular Weight: | |
| DrugBank Indication: | Trastuzumab deruxtecan is indicated for the treatment of adult patients with HER-2 positive breast cancer that is unresectable or metastatic and was previously treated with at least 2 anti-HER2-based regimens while the cancer was metastatic. Continued approval will depend on the results of clinical trial results confirming its clinical benefit. |
| DrugBank Pharmacology: | Trastuzumab demonstrates antitumor activity against certain types of HER2 positive breast cancer, however, clinical trials are still ongoing to confirm its efficacy. By exploiting both targeted antibody and cytotoxic effects, trastuzumab deruxtecan can effectively destroy tumors. The FDA label warns of a potential risk for neutropenia, interstitial lung disease/pneumonitis, and left ventricular dysfunction following the use of this drug. |
| DrugBank MoA: | Trastuzumab deruxtecan is a humanized anti-HER2 IgG1 antibody, targeting cancer cause by mutation of the HER2 gene. In addition, the small molecule portion of this drug, deruxtecan (DXd), is a topoisomerase I inhibitor. It is attached to the antibody by a peptide linker. After trastuzumab deruxtecan binds to HER2 found on malignant cells, it is internalized and linker cleavage occurs through the actions of lysosomal enzymes. After it is released through cleavage, DXd causes targeted DNA damage and apoptosis in cancer cells, due to the ability to cross cell membranes. Normally, drugs in this class (antibody-drug conjugates) present a challenge. The monoclonal antibody accurately targets cancer cells, however exert limited killing action. The addition of a cytotoxic agent (a topoisomerase I inhibitor in this case) effectively kills dividing cancer cells, including those in the healthy tissues, leading to various adverse effects. The peptide linker used to formulate this drug is cleavable, which is unique to other antibody-drug conjugates, allowing for increased efficacy and reduced drug resistance to topoisomerase. |
| Targets: | High affinity immunoglobulin gamma Fc receptor I antibody; DNA topoisomerase 1 inhibitor |
| Inclusion Criteria: | Therapeutic strategy associated |
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