Optically Active Azabicyclo Ring Derivative for Menin-MLL Inhibition
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Solution Overview
Problem
Current treatments for cancers associated with MLL fusion proteins, such as leukemia, lack effective medicaments that inhibit the binding between menin and MLL fusion proteins, and there is a need for improved therapeutic drugs and methods to target specific gene mutations in tumors.
Innovation Solution
A medicament comprising 5-fluoro-2-[(4-{7-[(1S,3S,4R)-5-methylidene-2-azabicyclo[2.2.2]octane-3-carbonyl]-2,7-diazaspiro[3.5]nonan-2-yl}pyrimidin-5-yl)oxy]-N,N-di(propan-2-yl)benzamide or its pharmaceutically acceptable salts, administered orally at various dosages, including combinations with other drugs, to inhibit this binding and enhance anticancer effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional cancer treatments are used, then cancer therapy is provided, but effective inhibition of menin-MLL fusion protein binding is not achieved
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of the azabicyclo ring derivative to optimize its binding affinity and selectivity for the menin-MLL fusion protein interaction. Specific structural parameters such as stereochemistry ((1S,3S,4R) configuration), substituent groups (pyrimidine-5-yl, carbonyl, diazaspiro), and molecular geometry are precisely controlled to enhance the inhibitor's ability to disrupt the menin-MLL complex, thereby achieving reliable anticancer effects through targeted binding inhibition.
2Reliability
If single agent therapy is used, then treatment simplicity is maintained, but anticancer effect enhancement is limited
Solution Approach 1:
The patent applies merging by combining the azabicyclo ring derivative with other anticancer agents to create combination therapy regimens. This strategy merges the specific binding inhibition mechanism of the derivative with complementary mechanisms of other cancer treatments, achieving synergistic anticancer effects that surpass single agent therapy while managing tumor progression through multi-target approaches.
Data Source
AI summary
The present invention relates to suitable usage, dosage, and use of an optically active azabicyclo ring derivative useful as a medicament, or a pharmaceutically acceptable salt thereof, and a pharmaceutical composition comprising it.