Phenylalanine LAT1 Inhibitors for Selective T-Cell Modulation
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Solution Overview
Problem
Current therapies for inflammatory diseases, autoimmune diseases, graft-vs-host disease, and solid organ transplant rejection are inadequate, and there is a need for novel treatments that target the Large Amino Acid Transporter 1 (LAT1) to modulate immune response and metabolism.
Innovation Solution
Development of substituted phenylalanine derivatives that act as LAT1 inhibitors, which can be administered to patients to treat these conditions by targeting the LAT1 transporter and modulating immune cell metabolism.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used for inflammatory diseases and autoimmune diseases, then treatment is provided, but the therapies are inadequate and do not effectively modulate immune response
Solution Approach 1:
The patent applies parameter changes by developing novel substituted phenylalanine derivative compounds with specific molecular structures (Formulas 1-3) that have optimized pharmacological parameters. These compounds exhibit improved potency, selectivity, and metabolic stability compared to current therapies, enabling effective LAT1 inhibition and immune response modulation in inflammatory and autoimmune diseases
Solution Approach 2:
The patent introduces LAT1 inhibitors as intermediary compounds that mediate between the therapeutic goal and the underlying pathophysiology. These compounds selectively inhibit the Large Neutral Amino Acid Transporter 1, thereby modulating immune cell metabolism and function as an intermediary mechanism to treat inflammatory and autoimmune diseases
2Adaptability or versatility
If LAT1 inhibitors are developed to treat inflammatory diseases, then immune response modulation is achieved, but novel treatments with improved drug-like properties are needed
Solution Approach 1:
The patent optimizes drug-like properties by systematically varying molecular parameters of the phenylalanine derivatives, including substituent groups (R1-R5), stereochemistry, and functional groups. This enables optimization of pharmacokinetic parameters such as solubility, permeability, metabolic stability, and protein binding while maintaining LAT1 inhibitory activity
Solution Approach 2:
The patent employs composite molecular structures combining phenylalanine core with various substituent groups (aromatic, aliphatic, heterocyclic moieties) to create compounds with enhanced drug-like properties. These composite structures provide improved pharmacokinetic profiles and therapeutic indices
Data Source
AI summary
Phenylalanine-based inhibitors of the Large Amino Acid Transporter 1 (LAT1) are disclosed. The compounds are useful in modulating the transcellular transport of substrates of LAT1 such as large neutral amino acids. The compounds are useful in immunomodulation therapies.