Cycloalkane-1,3-Diamine Compounds Blocking Menin-MLL Binding
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Solution Overview
Problem
Current treatments for leukemias involving chromosomal translocations of the MLL gene, such as infant leukemia, are not sufficiently effective, and there is a need for a drug that inhibits the interaction between menin and the MLL fusion protein to prevent abnormal cell growth and gene activation.
Innovation Solution
Development of novel low-molecular compounds with specific structures that inhibit the interaction between menin and the MLL protein, offering potential therapeutic and prophylactic benefits for diseases dependent on this interaction.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If standard treatment methods are used for leukemia with MLL gene mutation, then current therapy protocols are applied, but treatment effectiveness is insufficient
Solution Approach 1:
The patent extracts and targets the specific pathological interaction between menin and MLL fusion protein, separating this critical path from other leukemia treatment mechanisms. By designing compounds that specifically bind to the menin-MLL interface, the invention isolates and disrupts the key driver of abnormal gene activation, thereby improving treatment effectiveness for MLL-rearranged leukemias where standard therapies fail
Solution Approach 2:
The patent introduces low-molecular compounds as intermediary substances that mediate between menin and MLL fusion protein. These compounds act as molecular mediators that bind to the menin-MLL interaction interface, preventing direct protein-protein binding. The intermediary compound structure allows for selective disruption of the pathological complex formation, blocking abnormal transcriptional activation without affecting other cellular processes
2Productivity
If MLL fusion protein permanently activates gene clusters, then abnormal cell growth is triggered, but cell differentiation is inhibited
Solution Approach 1:
The patent applies preliminary anti-action by preventing the formation of the menin-MLL fusion protein complex before it can activate gene clusters and trigger abnormal cell growth. The low-molecular compounds bind to menin and block its interaction with MLL fusion protein, thereby preemptively preventing the transcriptional activation of HOX and MEIS1 genes. This preliminary blockade stops the pathological cascade at its origin, allowing normal cell differentiation programs to resume
Data Source
AI summary
The present invention provides a compound or a pharmaceutically acceptable salt thereof having an inhibitory action on the interaction between menin and an MLL protein. The compound represented by the formula (1) or a pharmaceutically acceptable salt thereof.wherein, in the formula (1), the dotted circle, R1, R2, R3, R4, R5, R6, R7, R8, Ring Q1, W, m and n are each as defined in the description.