Tumor Treatment Composition Combining Compound I With MEK Inhibition
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Solution Overview
Problem
Existing combinations of ICG001 and MEK inhibitors do not provide sufficient suppression of tumor growth, and there is a lack of known therapies involving the compound represented by formula (I) and MEK inhibitors.
Innovation Solution
The combined administration of (6S,9aS)-N-benzyl-8-({6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-1-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide or its pharmaceutically acceptable salts with MEK inhibitors, such as Trametinib, enhances antitumor effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If ICG001 and MEK inhibitor are used in combination, then antitumor effect is enhanced compared to single administration, but the suppression effect is still not sufficient
Solution Approach 1:
The patent changes the chemical parameter by replacing ICG001 with a structurally modified compound (formula I) that has enhanced Wnt pathway inhibition capability. This parameter change in the inhibitor's molecular structure leads to improved antitumor efficacy when combined with MEK inhibitors, resolving the insufficiency of the ICG001+MEK inhibitor combination.
Solution Approach 2:
The patent creates a composite therapeutic approach by combining a Wnt pathway inhibitor (formula I) with a MEK inhibitor. This composite therapy targets two different signaling pathways (Wnt and RAS-RAF-MEK-ERK) simultaneously, achieving synergistic antitumor effects that overcome the limitations of single-pathway or previous combination therapies.
2Adaptability or versatility
If there is no known combination therapy using compound (I) and MEK inhibitor, then treatment options are limited, but developing new combinations increases complexity
Solution Approach 1:
The patent segments the cancer therapy approach by separately targeting the Wnt pathway (with compound I) and the RAS-RAF-MEK-ERK pathway (with MEK inhibitor). This segmentation allows each component to be optimized independently while maintaining manageable complexity in the overall combination therapy regimen.
Data Source
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AI summary
Disclosed is a pharmaceutical composition for treating tumors, which comprises (6S,9aS)-N-benzyl-8-({6-[3-(4-ethylpiperazin-1-yl)azetidin-1-yl]pyridin-2-yl}methyl)-6-(2-fluoro-4-hydroxybenzyl)-4,7-dioxo-2-(prop-2-en-l-yl)hexahydro-2H-pyrazino[2,1-c][1,2,4]triazine-1(6H)-carboxamide represented by formula (I) or a pharmaceutically acceptable salt thereof and is administered in combination with an MEK inhibitor.