Pan-K-Ras Inhibitor Targets Multiple Mutations

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Solution Overview

Problem

Current treatments for K-Ras mediated cancers are limited, with a need for new inhibitors that can effectively target multiple forms of the K-Ras protein, including wild-type and mutant types, to address the unmet medical need for broader therapeutic options.

Innovation Solution

A compound of Formula (IB) and its stereoisomers, pharmaceutically acceptable salts, prodrugs, deuterated molecules, and conjugated forms are developed for use in pharmaceutical compositions to treat cancers associated with K-Ras G12C, G12D, G12V, G13D, G12R, G12S, G12A, Q61H mutations, and wild-type amplification by inhibiting K-Ras activity.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Adaptability or versatility

If multiple K-Ras inhibitors are developed to target various K-Ras mutants, then the coverage of patient populations is improved, but the complexity of drug discovery and development increases

Engineering Contradiction:

Improvecoverage of patient populationsVSAvoidcomplexity of drug discovery

Core Design Contradiction:

Adaptability or versatilityVSDevice complexity

Solution Approach 1:

The patent describes a compound of Formula (I) that functions as a pan-K-Ras inhibitor, capable of targeting multiple K-Ras mutant forms (G12C, G12D, G12V, G13D, G12R, G12S, G12A, Q61H) and wild-type K-Ras simultaneously. This multi-functional approach allows a single compound to address broad patient populations across different cancer types, resolving the contradiction by achieving versatility without requiring multiple separate drug development programs

Inventive Principle:

Principle #6Universality (Multi-functionality)

2Measurement precision

If K-Ras inhibitors are designed to target specific mutant alleles, then the specificity of treatment is improved, but the applicability to broader patient groups deteriorates

Engineering Contradiction:

Improvespecificity of treatmentVSAvoidapplicability to patient groups

Core Design Contradiction:

Measurement precisionVSAdaptability or versatility

Solution Approach 1:

The compound of Formula (I) is designed with a molecular structure that enables it to bind to and inhibit multiple K-Ras protein variants simultaneously. The invention achieves broad applicability across different K-Ras mutations and wild-type forms while maintaining effective inhibition of each specific mutant, thus resolving the contradiction between treatment specificity and patient group applicability

Inventive Principle:

Principle #6Universality (Multi-functionality)

3Reliability

If new K-Ras inhibitors are developed to address unmet medical needs, then the therapeutic options are improved, but the time and resources required for development increase

Engineering Contradiction:

Improvetherapeutic optionsVSAvoiddevelopment time

Core Design Contradiction:

ReliabilityVSLoss of time

Solution Approach 1:

The patent presents a previously undisclosed compound of Formula (I) that has been pre-validated as an effective pan-K-Ras inhibitor. By providing this ready-to-use molecular structure with demonstrated activity against multiple K-Ras forms, the invention eliminates the need for extensive preliminary screening and optimization phases, thereby reducing development time while delivering reliable therapeutic options for K-Ras mediated cancers

Inventive Principle:

Principle #10Preliminary action

Data Source

PatentUS20240376128A1N-cyclopropylpyrido [4, 3-d] pyrimidin-4-amine derivatives and uses thereof

Publication Date: 2024.11.14 JACOBIO PHARMACEUTICALS CO LTD

AI summary

Provided herein is a compound of Formula (IB), a stereoisomer thereof, a pharmaceutically acceptable salt thereof, a pharmaceutically acceptable salt of the stereoisomer thereof, a prodrug thereof, a deuterated molecule thereof or a conjugated form thereof; composition containing the same and the use thereof.