CD97-GSDME Interaction Inhibitor for Tumor Pyroptosis Sensitization
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Solution Overview
Problem
Malignant tumors with positive GSDME expression exhibit resistance to chemotherapy and immunotherapy, and CD97 plays a role in tumor differentiation, migration, and metastasis, complicating treatment.
Innovation Solution
A compound inhibiting the interaction between CD97 and GSDME is developed, enhancing tumor cell susceptibility to NK cell-induced pyroptosis and immune response, thereby sensitizing tumors to chemotherapy and immunotherapy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapeutic drugs are used to treat malignant tumors, then tumor growth can be inhibited, but tumor cell resistance to chemotherapy emerges
Solution Approach 1:
The compound WXLL-5471 is administered before chemotherapy to pre-sensitize tumor cells by inhibiting the CD97-GSDME interaction. This preliminary action prevents the development of drug resistance by blocking the protective pathway that tumor cells would otherwise use to survive chemotherapy, thereby improving the reliability of chemotherapy while preventing adaptability issues.
Solution Approach 2:
The compound WXLL-5471 acts as an intermediary substance that blocks the interaction between CD97 and GSDME proteins. By introducing this intermediary inhibitor, the patent prevents the harmful signaling pathway that leads to drug resistance, allowing chemotherapy to work effectively without triggering adaptive resistance mechanisms in tumor cells.
2Productivity
If CD97 is highly expressed in tumor cells, then tumor migration and metastasis are enhanced, but tumor cell susceptibility to immune killing is reduced
Solution Approach 1:
The compound WXLL-5471 specifically extracts or removes the protective function of the CD97-GSDME interaction pathway. By selectively inhibiting this specific protein-protein interaction, the patent eliminates the mechanism by which CD97 protects tumor cells from immune killing, thereby restoring immune susceptibility without broadly affecting other tumor cell functions.
Solution Approach 2:
The compound serves as an intermediary that disrupts the protective interaction between CD97 and GSDME. This intermediary inhibitor specifically targets the harmful interaction that prevents immune killing, allowing immune cells to effectively kill tumor cells even when CD97 is highly expressed and promoting metastasis.
3Strength
If GSDME is cleaved by Caspase-3 or GZMB to induce pyroptosis, then tumor cell death is achieved, but tumor resistance to therapy develops
Solution Approach 1:
The compound WXLL-5471 is administered in advance to block the CD97-GSDME interaction, preventing the protective effect that would otherwise allow tumor cells to resist pyroptosis. By taking this preliminary action, the patent ensures that when Caspase-3 or GZMB cleave GSDME to induce pyroptosis, the tumor cells cannot develop resistance through the CD97-mediated protective pathway.
Solution Approach 2:
The compound acts as an intermediary inhibitor that blocks the interaction between CD97 and GSDME, preventing the protective signaling that would allow tumor cells to survive pyroptotic cell death. This intermediary blocks the resistance pathway, ensuring that GSDME cleavage reliably induces tumor cell death without triggering resistance.
Data Source
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AI summary
The disclosure belongs to the technical field of medicine. Provided are a CD97 and GSDME interaction inhibitor having anti-tumor activity and an application thereof. A compound screened in the disclosure enhances the susceptibility of NK cells to kill tumor cells by inhibiting the interaction between GSDME and CD97 in tumor cells, so as to induce an immune anti-tumor effect. Moreover, the compound enhances the susceptibility of tumor cells to pyroptosis by blocking the protective effect of CD97 on cleavage of GSDME proteins. Therefore, the compound can be used for treating GSDME and CD97 double-positive malignant tumors, and combined chemotherapy, immunotherapy, etc., to enhance the susceptibility of malignant tumors to chemotherapy and immunotherapy, prolonging the overall survival period of patients with malignant tumors. Specifically provided is a compound having a structure set forth in formula (I), a pharmaceutically acceptable salt, a solvent compound or a deuterated compound thereof.