Cancer Treatment Compounds Targeting APC/C for Mitotic Arrest
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Solution Overview
Problem
Current cancer treatments that target mitotic progression often interact with microtubules, leading to resistance in some tumors, necessitating the development of drugs that can disrupt mitotic progression without affecting microtubules.
Innovation Solution
Compounds of Formulas (I), (II), and (III) are administered to induce mitotic arrest or inhibit the anaphase promoting complex/cyclosome (APC/C) activity, targeting mitotic progression and pre-replication complex licensing to treat various cancers, including those resistant to paclitaxel.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If microtubule disrupting drugs are used to target mitotic progression, then cancer cell division is disrupted, but tumors develop resistance through inactivation of the spindle checkpoint
Solution Approach 1:
The invention extracts the mitotic disruption function from microtubule interaction and relocates it to a different target (APC/C complex or pre-replication complex licensing). This allows achieving the same therapeutic effect (mitotic arrest) through an alternative pathway that does not involve microtubules, thereby avoiding the resistance mechanism that develops against microtubule-targeting drugs
Solution Approach 2:
The invention changes the molecular target parameter from microtubules to either the APC/C complex or pre-replication complex licensing mechanisms. This parameter change in the target of action allows the drug to disrupt mitosis through a different biochemical pathway, preventing the development of resistance that occurs when tumors adapt to microtubule disruption
2Adaptability or versatility
If drugs target mitotic progression without affecting microtubules, then treatment resistance is decreased, but the mechanism of action becomes more complex
Solution Approach 1:
The invention introduces an intermediary target (APC/C complex or pre-replication complex) that mediates the disruption of mitotic progression. Instead of directly targeting microtubules, the drug acts on this intermediary regulatory complex, which then indirectly disrupts mitosis by preventing proper chromosome segregation or cell cycle progression, thereby achieving resistance overcoming through a more complex but controllable mechanism
Data Source
AI summary
Some embodiments of this invention include methods for treating disease and methods for administering a compound of the invention. In some aspects of the invention, diseases can be treated by administration of compositions comprising a compound of the invention. Pharmaceutical compositions of some embodiments of the present invention comprise a compound of the invention.