RIPK1 Inhibitor Compounds for Inflammation and Apoptosis Modulation
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Solution Overview
Problem
Dysregulation of receptor-interacting protein kinase 1 signaling leads to excessive inflammation or cell death, contributing to various human diseases, and existing therapies are inadequate in effectively modulating these pathways.
Innovation Solution
Development of compounds that inhibit receptor-interacting protein kinase 1, which are used in pharmaceutical compositions to treat diseases mediated by this kinase, including inflammatory and neurodegenerative disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing therapies are used to modulate receptor-interacting protein kinase 1 signaling, then treatment is provided, but the therapies are inadequate in effectively controlling inflammation and cell death pathways
Solution Approach 1:
The patent applies parameter changes by developing compounds with specific molecular structures (Formula I) that target receptor-interacting protein kinase 1 with improved binding affinity and selectivity. The compounds feature variable substituents (R1-R6, A, L, Y1, Y2, X1, X2) that can be optimized to enhance therapeutic effectiveness while maintaining safety profiles, directly addressing the inadequacy of existing therapies.
2Object-affected harmful factors
If receptor-interacting protein kinase 1 activity is inhibited, then inflammatory responses and cell death are reduced, but dysregulation can lead to excessive inflammation or cell death
Solution Approach 1:
The patent incorporates feedback mechanisms through the design of compounds that selectively inhibit receptor-interacting protein kinase 1 while preserving other signaling pathways. The selective inhibition allows the body's natural feedback loops to maintain appropriate inflammatory and cell death responses, preventing excessive suppression while still treating the disease condition.
3Adaptability or versatility
If compounds are developed to inhibit receptor-interacting protein kinase 1, then therapeutic benefits are achieved for multiple diseases, but the complexity of regulatory mechanisms (ubiquitylation, deubiquitylation, phosphorylation) makes effective inhibition challenging
Solution Approach 1:
The patent applies the extraction principle by focusing specifically on the kinase activity of receptor-interacting protein kinase 1 as the primary target for inhibition. By extracting and targeting this specific enzymatic function while acknowledging the complex regulatory mechanisms (ubiquitylation, deubiquitylation, phosphorylation) as secondary pathways, the compounds achieve broad therapeutic benefits across multiple diseases without being overwhelmed by the full complexity of the regulatory network.
Data Source
AI summary
The present disclosure relates generally to compounds and compositions, and their use as kinase inhibitors.