CD73 Inhibitor Compounds Modulating Extracellular Adenosine
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Solution Overview
Problem
Current treatments for cancer and other disorders mediated by CD73, such as immunosuppressive and inflammatory conditions, lack effective inhibitors that can specifically target CD73 enzymatic activity to modulate extracellular adenosine levels and immune responses.
Innovation Solution
Development of compounds and compositions that inhibit CD73 enzymatic activity, including specific chemical formulas and pharmaceutical compositions, to reduce immunosuppressive and anti-inflammatory activities, thereby treating or preventing CD73-associated diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If CD73 enzymatic activity is inhibited to reduce extracellular adenosine levels, then tumor growth and metastasis are suppressed and immune responses are enhanced, but the development of specific and effective CD73 inhibitors remains challenging due to lack of potent compounds
Solution Approach 1:
The patent applies parameter changes by systematically modifying chemical structures of adenosine analogs, specifically varying substituents at different positions (R1-R6 groups) to optimize binding affinity and enzymatic inhibition potency. This involves changing molecular parameters such as substituent types, positions, and configurations to achieve potent CD73 inhibition while maintaining selectivity
Solution Approach 2:
The patent applies local quality by introducing specific functional groups at particular positions on the adenosine core structure. Different substituents (halogens, alkyl groups, heterocyclic rings) are placed at specific locations (positions 2, 6, N6, etc.) to create localized interactions with the CD73 active site, enhancing inhibition while preserving overall molecular recognition
2Adaptability or versatility
If current treatments are used for CD73-associated diseases, then some therapeutic effects may be achieved, but they lack the ability to specifically target CD73 enzymatic activity to effectively modulate extracellular adenosine levels and immune responses
Solution Approach 1:
The patent applies the intermediary principle by using adenosine analogs as mediator molecules that specifically bind to the CD73 enzyme active site. These analogs mimic the natural substrate adenosine but with modified properties that enhance binding affinity and inhibition potency, serving as selective intermediaries to block CD73-mediated adenosine production without affecting other cellular processes
Solution Approach 2:
The patent applies taking out by extracting the essential functional features of adenosine that are required for CD73 binding and inhibition. The core adenosine structure is retained while non-essential or detrimental parts are removed or replaced, creating simplified yet potent inhibitor molecules that specifically target CD73 enzymatic activity
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The compounds effectively inhibit CD73 activity, leading to modulation of extracellular adenosine levels and improved treatment outcomes for cancer, fibrosis, neurological disorders, and immune-related conditions by enhancing immune responses and reducing tumor growth and metastasis.
Implementation Method 1
These enzymes hydrolyze a variety of extracellular nucleotides to nucleosides including adenosine. Adenosine 5′-monophosphate (AMP) is a major substrate of CD73 that is hydrolyzed to adenosine.
Implementation Method 2
Development of compounds and compositions that inhibit CD73 enzymatic activity, including specific chemical formulas and pharmaceutical compositions, to reduce immunosuppressive and anti-inflammatory activities
Data Source
AI summary
CD73 (also known as ecto-5′-nucleotidase) inhibitor compounds are provided, as well as compositions and uses thereof for treating or preventing CD73-associated or related diseases, disorders and conditions, including cancer- and immune-related disorders. CD73 inhibitor compounds include compounds having the structure set forth in Formula I′ and pharmaceutically acceptable esters or salts thereof.