Selective CDK2 Inhibitors for Aberrant DNA Replication Control

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Solution Overview

Problem

There is a need for the development of compounds capable of inhibiting the activity of Cyclin-dependent kinase 2 (CDK2) and its complexes to prevent aberrant DNA replication and treat associated diseases or disorders, particularly cancer, as overactivity of CDK2/cyclin complexes leads to cell cycle dysregulation and cancer development.

Innovation Solution

The development of compounds that bind and inhibit CDK2/cyclin complexes, specifically targeting CDK2/cyclin E and/or CDK2/cyclin A complexes, to prevent aberrant DNA replication and treat CDK2-related diseases or disorders.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Object-affected harmful factors

If CDK2/cyclin complexes are inhibited to prevent aberrant DNA replication, then cancer development is treated, but cell cycle progression is disrupted

Engineering Contradiction:

Improveaberrant DNA replicationVSAvoidcell cycle progression

Core Design Contradiction:

Object-affected harmful factorsVSStability of the object's composition

Solution Approach 1:

The patent employs selective inhibition of CDK2/cyclin E and CDK2/cyclin A complexes specifically in cancer cells with CCNE1 or CCNE2 amplification, rather than broadly inhibiting all cell cycle kinases. This localized approach targets the harmful aberrant DNA replication in malignant cells while minimizing disruption to normal cell cycle progression in healthy tissues.

Inventive Principle:

Principle #3Local quality

Solution Approach 2:

The invention utilizes compounds with specific molecular structures (Formula I and II) that exhibit optimal binding affinity and selectivity parameters for CDK2/cyclin complexes. By carefully tuning the chemical parameters of the inhibitors, the patent achieves effective suppression of aberrant DNA replication while maintaining appropriate cell cycle regulation in normal cells.

Inventive Principle:

Principle #35Parameter changes

2Reliability

If selective inhibition of CDK2/cyclin E and CDK2/cyclin A complexes is achieved, then therapeutic specificity is improved, but compound design complexity increases

Engineering Contradiction:

Improvetherapeutic specificityVSAvoidcompound design

Core Design Contradiction:

ReliabilityVSDevice complexity

Solution Approach 1:

The patent divides the complex task of achieving selective CDK2 inhibition into manageable structural components defined in Formula I and II. The molecular design is segmented into specific substituents (R1-R6, L1-L3) that can be independently optimized to achieve the desired selectivity for CDK2/cyclin E and CDK2/cyclin A complexes while simplifying the overall drug design process.

Inventive Principle:

Principle #1Segmentation

Data Source

PatentUS20260014146A1CDK2 inhibitors and methods of using the same

Publication Date: 2026.01.15 CEDILLA THERAPEUTICS INC

AI summary

The present disclosure provides compounds, compositions thereof, and methods of using the same for the inhibition of CDK2, and the treatment of CDK2 related diseases and disorders.