Selective S1P Receptor Modulators for Immune Disorders
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Solution Overview
Problem
Current therapies lack effective modulators for S1P receptors, which are crucial for treating various diseases due to their tissue- and response-specificity, including cancer, autoimmune disorders, and transplant rejection, with existing treatments often resulting in unwanted side effects.
Innovation Solution
Development of new S1P receptor modulators, including agonists, partial agonists, and antagonists, represented by specific chemical compounds that selectively target S1P receptors to modulate their activity, thereby treating or preventing conditions such as cancer, autoimmune disorders, and transplant rejection with reduced side effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies are used to treat diseases associated with S1P receptor activity, then treatment of conditions like cancer, autoimmune disorders, and transplant rejection can be achieved, but unwanted side effects occur due to lack of selectivity
Solution Approach 1:
The patent applies local quality by designing compounds with specific molecular structures (formula I) that selectively bind to particular S1P receptor subtypes (S1P1, S1P2, S1P3, S1P4, or S1P5). This selectivity ensures that therapeutic effects are localized to specific receptor-mediated pathways, treating diseases like cancer, autoimmune disorders, and transplant rejection while minimizing off-target side effects through precise receptor targeting
2Object-affected harmful factors
If S1P receptor modulators are developed to achieve tissue- and response-specificity, then unwanted side effects can be reduced, but the complexity of developing selective compounds increases
Solution Approach 1:
The patent employs parameter changes by systematically varying molecular parameters in the compounds of formula I, including different substituents (R1-R6), ring structures (A and B), and linker variations. These parameter modifications enable fine-tuning of receptor selectivity and affinity, allowing developers to optimize compounds for specific S1P receptor subtypes while managing development complexity through structured molecular design
Solution Approach 2:
The patent demonstrates universality by creating a versatile compound platform (formula I) that can target multiple S1P receptor subtypes (S1P1-S1P5) with a single molecular framework. This multi-functional approach allows the same core structure to be adapted for different therapeutic indications and receptor targets, reducing overall development complexity through a unified design strategy
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The S1P receptor modulators effectively treat or prevent a range of diseases by selectively targeting S1P receptors, reducing side effects and improving treatment outcomes for conditions like cancer, autoimmune disorders, and transplant rejection.
Implementation Method 1
S1P signals cells in part via a set of G protein-coupled receptors named S1P1, S1P2, S1P3, S1P4, and S1P5
Implementation Method 2
A conformational shift is induced in the G-Protein Coupled Receptor (GPCR) when the ligand binds to that receptor
Implementation Method 3
Eventually the GTP on the G-proteins is hydrolyzed to GDP, and the subunits of the G-proteins re-associate with each other and then with the receptor
Implementation Method 4
Amplification plays a major role in the general GPCR pathway. The binding of one ligand to one receptor leads to the activation of many G-proteins, each capable of associating with many effector proteins, leading to an amplified cellular response
Implementation Method 5
Tissue specificity of the S1P receptors is important, because development of an agonist or antagonist selective for one receptor localizes the cellular response to tissues containing that receptor, limiting unwanted side effects
Data Source
AI summary
The present invention relates to amides that have activity as SlP receptor modulating agents and the use of such compounds to treat diseases associated with inappropriate SlP receptor activity. The compounds may be used as immunomodulators, e.g., for treating or preventing diseases such as autoimmune and related immune disorders including systemic lupus erythematosus, inflammatory bowel diseases such as Crohn's disease and ulcerative colitis, type I diabetes, uveitis, psoriasis, myasthenia gravis, rheumatoid arthritis, non- glomerular nephrosis, hepatitis, Behcet's disease, glomerulonephritis, chronic thrombocytopenic purpura, hemolytic anemia, hepatitis and Wegner's granuloma; and for treating other conditions.