Small Molecule PD-L1 Expression Inhibitor for Oral Immune Therapy
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Solution Overview
Problem
Current treatments for diseases associated with reduced immune function caused by PD-1/PD-L1 binding, such as cancer and infections, lack effective oral and cost-efficient small molecule inhibitors.
Innovation Solution
Development of a 1-benzoyl-N-(4-phenoxyphenyl)piperidine-3-carboxamide compound that inhibits PD-L1 expression and reduces IL-2 production, offering a novel approach as an immune checkpoint inhibitor.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If antibody drugs (nivolumab, pembrolizumab, atezolizumab, durvalumab) are used as immune checkpoint inhibitors, then the inhibitory effect on PD-1/PD-L1 binding is achieved, but the administration route is limited to injection and the cost is high
Solution Approach 1:
The patent replaces the biological mechanism of antibody drugs with a small molecule compound mechanism. The compound of formula (I) acts as a PD-L1 expression inhibitor through small molecule interaction, substituting the large molecule antibody mechanism with a smaller, orally administrable chemical structure that achieves similar immune checkpoint inhibition effects
Solution Approach 2:
The patent changes the molecular size and chemical structure parameters from antibody drugs to small molecule compounds. This parameter change enables oral administration and reduces cost while maintaining the therapeutic effect of inhibiting PD-L1 expression and blocking PD-1/PD-L1 binding
2Ease of operation
If small molecule compounds are developed as immune checkpoint inhibitors, then the oral administration and cost efficiency are improved, but no effective small molecule compound targeting PD-1 or PD-L1 has been known yet
Solution Approach 1:
The patent develops a small molecule compound that is chemically synthesized and can be produced at lower cost compared to expensive antibody drugs. The compound structure of formula (I) allows for scalable chemical manufacturing, making it a cost-effective alternative to biologically produced antibodies
3Reliability
If PD-L1 expression is inhibited to treat cancer and infections, then the immune function is enhanced, but the mechanism of PD-L1 expression suppression needs to be targeted
Solution Approach 1:
The patent takes preliminary action by inhibiting PD-L1 expression before the PD-1/PD-L1 binding can occur. The compound of formula (I) suppresses PD-L1 expression at the transcriptional or translational level, preventing the formation of the inhibitory complex before it can suppress T-cell function
Solution Approach 2:
The patent introduces a small molecule compound as an intermediary that mediates the inhibition of PD-L1 expression. This intermediary compound binds to cellular targets (such as transcription factors or signaling molecules) to suppress PD-L1 expression, providing a controllable and specific mechanism for immune enhancement
Data Source
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AI summary
The present invention provides a compound of formula (I): or a pharmaceutically acceptable salt thereof, wherein R1, R2, m and n are as defined in the specification, with an inhibitory effect of PD-L1 expression and an inhibitory effect of reduced production of IL-2 and a medicament useful for the treatment of a disease associated with the reduced immune function caused by the formation of PD-1/PD-L1 binding.