TRPC5 Small-Molecule Modulators for Proteinuria Control

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Solution Overview

Problem

There is a need for more effective methods to treat or reduce the risk of developing kidney diseases such as proteinuria, as well as other conditions like anxiety, depression, and cancer, as existing treatments have high relapse frequencies and significant side effects.

Innovation Solution

Development of small molecule modulators, specifically inhibitors and agonists, of the Transient Receptor Potential Cation Channel, subfamily C, member 5 (TRPC5), which can be administered to subjects to treat or reduce the risk of developing these conditions by modulating TRPC5 activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If existing treatments for kidney disease are used, then proteinuria can be reduced, but relapse frequency is extremely high and side effects are significant

Engineering Contradiction:

Improvetreatment effectivenessVSAvoidside effects and relapse

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent changes the molecular target parameter from traditional kidney disease treatments to TRPC5 channels, using small molecule modulators that specifically inhibit TRPC5 activity. This parameter change in the therapeutic target leads to reduced proteinuria with lower relapse frequency and fewer side effects compared to existing treatments.

Inventive Principle:

Principle #35Parameter changes

Solution Approach 2:

The patent introduces small molecule TRPC5 modulators as intermediary substances that mediate the treatment effect. These modulators bind to TRPC5 channels and inhibit their activity, thereby reducing proteinuria. The small molecules serve as the intermediary between the treatment and the disease mechanism, providing effective therapy with reduced harmful effects.

Inventive Principle:

Principle #24Intermediary (Mediator)

2Reliability

If TRPC5 activity is inhibited, then proteinuria is reduced, but the mechanism of action is not well understood

Engineering Contradiction:

Improvetherapeutic effectVSAvoidmechanism understanding

Core Design Contradiction:

ReliabilityVSLoss of information

Solution Approach 1:

The patent employs feedback mechanisms through FLIPR assays and other functional assays to test and validate TRPC5 modulator activity. These feedback loops allow continuous monitoring and verification of the modulators' effects on TRPC5 channels, providing both therapeutic validation and mechanistic insight into how the small molecules inhibit channel activity and reduce proteinuria.

Inventive Principle:

Principle #23Feedback

3Adaptability or versatility

If small molecule ligands are developed, then TRPC5 activity can be modulated, but determining agonist vs antagonist activity is complex

Engineering Contradiction:

ImproveTRPC5 modulation capabilityVSAvoidactivity determination process

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent replaces complex functional testing procedures with FLIPR assays that provide clear, quantifiable readouts for TRPC5 modulator activity. The FLIPR technology substitutes complex mechanistic testing with a streamlined fluorescent-based detection system that reliably distinguishes between agonist and antagonist activities, simplifying the characterization process while maintaining versatility.

Inventive Principle:

Principle #28Mechanics substitution (Replace mechanical system)

Data Source

PatentUS12466834B2Imidazodiazepinediones and methods of use thereof

Publication Date: 2025.11.11 GFB (ABC) LLC

AI summary

Disclosed are compounds according to Formula (I) or (II), and pharmaceutical compositions comprising them. Also disclosed are therapeutic methods, e.g., of treating kidney diseases, using the compounds of Formula (I) or (II).