2021 Fiscal Year Research-status Report
Reactivity of acrolein produced by cancer cells: Application to selective cancer therapy
| Project/Area Number |
21K05269
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| Research Institution | Tokyo Institute of Technology |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | Acrolein / Azide / Prodrug / Cycloaddition / Cancer |
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| Outline of Annual Research Achievements |
Cytotoxic anticancer drugs are not genuinely selective for cancer cells but could also significantly affect healthy cells. Prodrug therapy provides an alternative approach using a less cytotoxic form of anticancer drugs. It involves the synthesis of inactive drug derivatives converted to an active form inside the body and, preferably, only at the site of cancerous tissues, thereby reducing the adverse drug reaction events. However, the prodrug release strategies used thus far have their drawbacks. We proposed the prodrug activation approach by utilizing the reaction between aryl azide and endogenous acrolein, an endogenous metabolite that is overproduced by cancer cells.
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| Current Status of Research Progress |
Current Status of Research Progress
1: Research has progressed more than it was originally planned.
Reason
In FY2021, we designed a prodrug having a self-immolation linker that could efficiently release the drugs by reacting with acrolein. We established an effective method to introduce the anticancer compound to the prodrug. In addition, the prodrug molecules were tested on cancer cells and mouse models. As a result, we confirmed that the prodrug molecule showed remarkable therapeutic effects even when it was injected intratumorally or intravenously into the mouse models.
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| Strategy for Future Research Activity |
Since we previously found that acrolein is highly produced in various types of cancer, we expect that our prodrug would be applicable to treat cancer. Therefore, in FY2022, we will prepare various aryl azide-based prodrugs and examine their efficacy in other types of cancer.
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