Indole Derivative TDO IDO Inhibitors Lower Kynurenine
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Solution Overview
Problem
Current treatments for various diseases, including cancer, inflammatory conditions, and CNS disorders, are limited by the immunosuppressive effects of tryptophan catabolism mediated by TDO and IDO, which hinder effective immune responses against pathogens and tumors.
Innovation Solution
Development of TDO and IDO inhibitors that prevent the conversion of tryptophan to N-formylkynurenine, thereby modulating tryptophan metabolism and reducing immunosuppressive kynurenine levels, allowing for enhanced immune responses against diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If TDO and IDO enzymes are active to regulate tryptophan metabolism, then tryptophan catabolism is maintained for immune regulation, but immunosuppressive kynurenine levels increase which hinders effective immune responses against pathogens and tumors
Solution Approach 1:
The patent extracts and removes the harmful immunosuppressive effect by developing specific inhibitors that block TDO and IDO enzyme activity, thereby preventing kynurenine production while maintaining tryptophan metabolism regulation
Solution Approach 2:
The patent converts the harmful immunosuppressive kynurenine pathway into a beneficial therapeutic target by using small molecule inhibitors to block this pathway, thereby transforming the immune-suppressing mechanism into an immune-enhancing treatment strategy for cancer and infectious diseases
2Reliability
If tryptophan catabolism is induced by inflammatory mediators to restrict excessive immune responses, then immunopathology is prevented, but in disease states this feedback loop hinders effective immune responses against tumors and pathogens
Solution Approach 1:
The patent applies preliminary anti-action by administering TDO and IDO inhibitors before or during disease progression to preemptively block the immunosuppressive kynurenine pathway, preventing the harmful feedback loop from developing and maintaining effective immune responses throughout the disease course
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 inhibitors effectively lower kynurenine levels, alleviating immunosuppression and potentially improving treatment outcomes for a wide range of diseases, including cancer, infectious diseases, and CNS disorders by restoring immune function.
Implementation Method 1
Both enzymes catalyze the oxidative cleavage of the 2,3 double bond in the indole ring, converting tryptophan to N-formylkynurenine
Data Source
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AI summary
Provided is a tryptophan-2,3-dioxygenase (TDO) and/or indoleamine-2,3-dioxygenase (IDO) inhibitor compound for use in medicine, which compound comprises the following formula: wherein X1, X2, X3, X4, and X5 may be the same or different and each is independently selected from C, N and O; each atom having a dotted line may independently have a double bond or a single bond, provided that valencies at each atom are maintained; each R1, R2, R3, R4, R5, and R7 may be present or absent and may be the same or different and is selected from H and a substituted or unsubstituted organic group, provided that the number of such R groups present is such that the valencies of X1, X2, X3, X4, and X5 are maintained; one or two R6 groups may be present and are selected from H and a substituted or unsubstituted organic group, provided that the number of R6 groups present is such that the valency of the carbon atom to which they are attached is maintained, and provided that at least one R6 is an organic group comprising an atom double-bonded to an oxygen atom (preferably a carbonyl group or a sulphonyl group) at an α-, β-, or γ-position to the carbon atom to which the R6 is attached and in which the atom double-bonded to an oxygen atom is also bonded to a hetero-atom.