Selective αvβ6 Integrin Compounds for Oral Administration
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Solution Overview
Problem
There is a notable absence of therapeutic success with orally bioavailable integrin inhibitors, despite the recognized role of integrins as drug targets for treating various human diseases, including inflammation, fibrosis, oncology, and vascular disease.
Innovation Solution
Development of compounds that selectively inhibit αvβ6 integrin, which are useful for treating conditions such as idiopathic pulmonary fibrosis, diabetic nephropathy, and other fibrotic and oncological diseases, through the administration of specific compounds that modulate integrin signaling.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If injectable integrin inhibitors are used, then therapeutic efficacy is achieved, but ease of operation deteriorates due to requiring injection rather than oral administration
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of integrin inhibitors to achieve oral bioavailability. Specifically, the compounds are designed with molecular weight between 200-800 Da, logP between 2-6, and specific functional groups that enable oral absorption while maintaining integrin binding affinity. This transforms the administration route from injectable to oral by changing physicochemical parameters of the inhibitor molecules.
2Adaptability or versatility
If broad-spectrum integrin inhibitors are developed, then versatility improves, but object-affected harmful factors worsen due to off-target effects on other integrin heterodimers
Solution Approach 1:
The patent applies local quality by designing compounds with selective affinity for specific integrin heterodimers (e.g., αvβ3, αvβ5, αvβ6) through tailored molecular structures. The inhibitors contain specific functional groups and spatial arrangements that match the binding pockets of target integrins, enabling selective inhibition of pathological integrins while sparing other heterodimers. This allows tissue-specific or disease-specific targeting without broad off-target effects.
3Adaptability or versatility
If new classes of integrin inhibitors are developed, then adaptability improves, but device complexity worsens due to need for novel chemical structures and synthesis methods
Solution Approach 1:
The patent applies universality by developing a platform of compounds with a core structural motif that can be modified to target different integrin heterodimers. The general formula encompasses multiple specific compounds that share a common pharmacophore, allowing a single synthesis platform to generate inhibitors for various integrins. This reduces overall complexity by using a universal molecular framework rather than developing entirely separate classes for each integrin target.
Data Source
AI summary
Disclosed are small molecule inhibitors of αvβ6 integrin, and methods of using them to treat a number of diseases and conditions.