LRRC8 Channel Modulation for Platelet Thrombosis Control

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Solution Overview

Problem

Current pharmacological strategies to prevent and treat cardiovascular thrombosis and platelet dysfunction are inadequate, leading to significant morbidity and mortality from conditions such as myocardial infarction, stroke, and thrombosis associated with cardiovascular medical devices, with limited efficacy and safety concerns, particularly in patients with Type 2 diabetes.

Innovation Solution

Administration of LRRC8 protein modulators, specifically DCPIB and its congeners, to regulate platelet function and inhibit thrombosis by targeting LRRC8 protein channels, which are essential for platelet activation and volume regulation.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If current pharmacological strategies (platelet enzyme inhibitors, agonist inhibitors, receptor inhibitors) are used to prevent thrombosis, then thrombosis prevention is achieved to some extent, but significant residual risk for morbidity and mortality persists

Engineering Contradiction:

Improvethrombosis prevention efficacyVSAvoidresidual risk for morbidity and mortality

Core Design Contradiction:

ReliabilityVSObject-affected harmful factors

Solution Approach 1:

The patent introduces LRRC8 protein channels as a new intermediary target between platelet activation and thrombosis formation. By modulating LRRC8 channels, the invention creates a novel pathway that complements existing antiplatelet therapies, thereby reducing residual thrombosis risk without increasing bleeding complications

Inventive Principle:

Principle #24Intermediary (Mediator)

Solution Approach 2:

The invention changes the therapeutic parameter by targeting LRRC8 protein channels instead of (or in addition to) traditional platelet enzymes or receptors. This parameter change enables a new mechanism of action that addresses residual thrombosis risk while maintaining safety

Inventive Principle:

Principle #35Parameter changes

2Reliability

If platelet activation is inhibited to prevent thrombosis, then thrombus formation is reduced, but bleeding complications may occur

Engineering Contradiction:

Improvethrombosis preventionVSAvoidbleeding complications

Core Design Contradiction:

ReliabilityVSObject-generated harmful factors

Solution Approach 1:

The patent applies local quality by selectively modulating LRRC8 channels in specific platelet subpopulations or activation states. This localized modulation allows thrombosis prevention in high-risk situations while preserving normal hemostatic function in others, thereby reducing bleeding complications

Inventive Principle:

Principle #3Local quality

Data Source

PatentUS20250339392A1The use of LRRC8 protein modulators to prevent and treat cardiovascular disease

Publication Date: 2025.11.06 SENSEION THERAPEUTICS INC

AI summary

The present invention is directed to various methods of for preventing and/or treating cardiovascular thrombosis, hereditary or acquired defects in platelet function, and hereditary or acquired thrombocytosis, wherein the method comprises administering a therapeutically effective amount of an LRRC8 protein modulator to the patient. Compounds that are LRRC8 protein modulators are also described, including DCPIB (4-[2[butyl-6,7-dichloro-2-cyclopentyl-2,3-dihydro-1-oxo-1H-inden-5-yl)oxy]butanoic acid).