Pyrimido-diazepinone Kinase Inhibitors for PI3K Selectivity
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Solution Overview
Problem
Current treatments for diseases mediated by phosphatidylinositol-4,5-bisphosphate 3-kinases (PI3K), such as cancer and inflammatory disorders, lack effective inhibitors that can selectively target PI3K-γ and PI3K-δ, leading to incomplete disease management.
Innovation Solution
Development of pyrimido-diazepinone compounds that act as selective inhibitors of PI3K-δ and/or PI3K-γ, potentially offering dual inhibition capabilities to address the misregulation of these kinases in various diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for PI3K-mediated diseases, then disease management is provided, but selectivity for PI3K-γ and PI3K-δ is insufficient leading to incomplete disease management
Solution Approach 1:
The patent applies local quality by designing the inhibitor molecule with specific functional groups and structural features that are optimized to interact with the unique binding pocket characteristics of PI3K-γ and PI3K-δ. The compound structure includes specific substituents and molecular arrangements that confer selectivity for these isoforms while maintaining inhibitory potency, addressing the need for both reliability in disease management and precision in kinase selectivity.
2Measurement precision
If selective inhibitors for PI3K-γ and PI3K-δ are developed, then kinase selectivity is improved, but treatment efficacy for reducing cell growth and tumor growth must be validated
Solution Approach 1:
The patent incorporates feedback by evaluating the therapeutic effectiveness of the selective PI3K-γ/δ inhibitors through multiple assessment methods including cell growth assays, tumor models, and biochemical activity measurements. This feedback loop ensures that the compounds not only achieve the desired kinase selectivity but also demonstrate reliable therapeutic effectiveness in reducing PI3K-mediated cell growth and tumor progression, thereby validating both selectivity and efficacy simultaneously.
Data Source
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AI summary
The present invention relates to use of pyrimido-diazepinone compounds that are able to modulate protein kinases such as ΡΙ3Κ-γ and PI3K-δ, which are members of the Class I Type IA and Class I Type IB family of phosphatidylinositol- 4,5-bisphosphate 3-kinases, and the use of such compounds in the treatment of various diseases, disorders or conditions.