IDO Inhibitor Compounds Blocking Tryptophan Degradation
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Solution Overview
Problem
Current treatments for IDO-related diseases, such as cancer, viral infections, and autoimmune disorders, are limited by the immunosuppressive effects of indoleamine 2,3-dioxygenase (IDO), which impede effective T-cell activation and tumor rejection, and there is a need for more effective inhibitors to enhance tryptophan metabolism and immune response.
Innovation Solution
Development of novel compounds, specifically inhibitors of the IDO enzyme, represented by formulas (Ia) and (Ib), which inhibit IDO activity, thereby preventing tryptophan degradation and enhancing T-cell activation and immune response, potentially used in combination with other therapeutic modalities.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If IDO activity is up-regulated to suppress T-cell responses and promote tolerance, then immune tolerance is enhanced, but T-cell activation and tumor rejection are impeded
Solution Approach 1:
The patent extracts and inhibits the specific IDO enzyme activity that causes immunosuppression, while preserving other immune functions. By using small molecule inhibitors to selectively block IDO's tryptophan catabolic activity, the patent removes the harmful immunosuppressive effect without affecting overall immune system functionality.
Solution Approach 2:
The patent changes the biochemical parameters of tryptophan metabolism by blocking IDO-mediated degradation. This prevents tryptophan depletion and maintains the biochemical environment necessary for T-cell activation and proliferation, thereby reversing the immunosuppressive state.
2Reliability
If IDO activity is increased to prevent fetal rejection, then fetal allograft survival is maintained, but T-cell-mediated immune responses are suppressed
Solution Approach 1:
The patent applies preliminary anti-action by using IDO inhibitors to counteract the immunosuppressive effects before they fully manifest. By blocking IDO activity, the patent prevents the depletion of tryptophan that would otherwise suppress T-cell responses, thereby maintaining immune surveillance capabilities.
3Object-affected harmful factors
If IDO is induced to exert antimicrobial effector mechanism, then pathogen growth is arrested, but tryptophan depletion occurs leading to wasting symptoms
Solution Approach 1:
The patent converts the harmful tryptophan depletion effect into a beneficial therapeutic outcome by using IDO inhibitors to block the catabolic pathway. This prevents the wasting symptoms associated with chronic tryptophan depletion while preserving the ability to mount effective immune responses against infections and malignancies.
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
These compounds effectively inhibit IDO activity, potentially treating or preventing IDO-associated diseases by enhancing T-cell activation, improving immune responses, and synergizing with conventional therapies to reduce tumor growth and viral infections.
Implementation Method 1
The enzyme indoleamine 2,3-dioxygenase (IDO) catalyzes the first and rate limiting step in the degradation of L-tryptophan to N-formyl-kynurenine
Data Source
AI summary
Disclosed herein are compounds of formula (I) which are inhibitors of an IDO enzyme:(I). Also disclosed herein are uses of the compounds in the potential treatment or prevention of an IDO-associated disease or disorder. Also disclosed herein are compositions comprising these compounds. Further disclosed herein are uses of the compositions in the potential treatment or prevention of an IDO-associated disease or disorder.