Indole CK2 Inhibitors Using Non-ATP Competitive Binding

Resolve Bottlenecks,
Find Innovative SolutionsGenerate Solutions

Solution Overview

Problem

Current kinase inhibitors for cancer treatment face issues such as side effects, resistance due to mutations, activation of alternative signaling pathways, DNA damage repair mechanisms, and lack of selectivity, particularly with the CK2 kinase target.

Innovation Solution

Development of indole derivatives that act as selective inhibitors of the protein kinase CK2, offering a non-ATP competitive mechanism to overcome resistance and improve therapeutic efficacy.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If ATP-competitive kinase inhibitors are used to treat cancer, then therapeutic efficacy is improved, but selectivity deteriorates due to high conservation of ATP site causing off-target effects

Engineering Contradiction:

Improvetherapeutic efficacyVSAvoidselectivity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

The patent inverts the conventional ATP-competitive inhibition approach by developing non-ATP competitive inhibitors that bind to alternative sites on the CK2 kinase. This inversion allows selective inhibition of CK2 without affecting other kinases that share the conserved ATP binding site, thereby resolving the contradiction between efficacy and selectivity

Inventive Principle:

Principle #13The other way round (Inversion)

Solution Approach 2:

The invention targets a specific local region (alternative binding site) on the CK2 kinase rather than the conserved ATP site. By designing inhibitors that bind to this unique local structure, the patent achieves high selectivity for CK2 while maintaining therapeutic efficacy against cancer

Inventive Principle:

Principle #3Local quality

2Reliability

If CK2 inhibitors are developed to avoid resistance, then resistance phenomena are reduced, but selectivity must be improved to avoid off-target effects

Engineering Contradiction:

Improveresistance preventionVSAvoidselectivity

Core Design Contradiction:

ReliabilityVSEase of manufacture

Solution Approach 1:

By inverting from ATP-competitive to non-ATP competitive inhibition mechanism, the patent simultaneously addresses both resistance prevention and selectivity. The alternative binding site is less prone to mutation-driven resistance, and the unique structural requirements for binding provide inherent selectivity

Inventive Principle:

Principle #13The other way round (Inversion)

Data Source

PatentUS12570632B2Indole derivatives and uses thereof for treating a cancer

Publication Date: 2026.03.10 UNIV CLAUDE BERNARD LYON 1

AI summary

The present invention relates to indole derivatives of formula (I′) as CK2 inhibitor and pharmaceutical compositions comprising the same. The present invention further relates to the use of such compounds of formula (I) for use for preventing and/or treating a cancer.