TDO IDO Inhibitor Compounds for Immunosuppression Relief
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Solution Overview
Problem
Current treatments for cancer, infectious diseases, and neurodegenerative disorders often fail to effectively target the immunosuppressive effects of tryptophan catabolism mediated by tryptophan-2,3-dioxygenase (TDO) and indoleamine-2,3-dioxygenase (IDO), which create an immunosuppressive environment that hampers immune responses against tumors and pathogens.
Innovation Solution
Development of TDO and IDO inhibitors that prevent the conversion of tryptophan to N-formylkynurenine, thereby disrupting the immunosuppressive kynurenine pathway and enhancing immune responses against cancer cells and pathogens.
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 physiological functions, but an immunosuppressive environment is created that hampers immune responses against tumors and pathogens
Solution Approach 1:
The patent extracts and removes the harmful immunosuppressive function by selectively inhibiting TDO and IDO enzymes. The compounds block the catalytic activity of these enzymes, preventing them from converting tryptophan to kynurenine, thereby extracting the immunosuppressive effect from the tryptophan metabolism pathway while preserving other physiological functions.
Solution Approach 2:
The patent changes the biochemical parameters of tryptophan metabolism by inhibiting the rate-limiting step catalyzed by TDO and IDO. This parameter change (blocking enzyme activity) shifts the metabolic flux, preventing kynurenine production and thereby altering the immunosuppressive microenvironment to support effective immune responses.
2Object-affected harmful factors
If tryptophan catabolism is induced by inflammatory mediators to restrict excessive immune responses, then immunopathology is prevented, but cancer treatments fail to effectively target the immunosuppressive effects
Solution Approach 1:
The patent applies inversion by reversing the physiological role of TDO and IDO. Instead of allowing these enzymes to suppress immune responses (their normal function), the compounds invert this effect by blocking enzyme activity, thereby converting the immunosuppressive pathway into an immunostimulatory state that enhances cancer treatment effectiveness.
Solution Approach 2:
The patent applies preliminary anti-action by pre-blocking TDO and IDO enzyme activity before cancer treatment. The inhibitors are administered to prevent the formation of immunosuppressive kynurenine metabolites in advance, creating a favorable immune environment that enhances the effectiveness of subsequent cancer therapies.
3Stability of the object's composition
If TDO and IDO enzymes catalyze tryptophan conversion to maintain physiological functions, then normal metabolism is preserved, but the immunosuppressive brake on the immune system prevents tumor elimination
Solution Approach 1:
The patent converts the harmful immunosuppressive function of TDO and IDO into a benefit. By inhibiting these enzymes, the compounds transform the normal metabolic pathway into a therapeutic mechanism that releases the immunosuppressive brake on the immune system, enabling effective tumor elimination while maintaining overall metabolic stability.
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, relieving the immunosuppressive brake on the immune system, allowing it to attack and eliminate tumors and pathogens, and can be used alone or in combination with other cancer therapies to improve treatment outcomes.
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 (I): wherein X1 is selected from C and N; X3 and X5 may be the same or different and each is independently selected from C, N, O and S; Y is selected from N and O; Z is selected from C, N and O; each bond represented by a dotted line may independently be a double bond or a single bond, provided that valencies at each ring atom are maintained and provided that the ring Q contains at least one double bond and provided that the atom N has a double bond; R3 and R5 may be present or absent and may be the same or different and each is independently selected from H and a substituted or unsubstituted organic group, provided that the number of R3 groups present is such that the valency of X3 is maintained, and the number of R5 groups present is such that the valency of X5 is maintained; each R11 and R12 may be present or absent and may be the same or different and each is independently selected from H and a substituted or unsubstituted organic group, provided that the number of R11 and R12 groups present is such that the valency of Z is maintained; R21 is selected from H and a substituted or unsubstituted organic group; R22 may be present or absent and is selected from H and a substituted or unsubstituted organic group; and Cy is a cyclic organic group.