CD73 Modulator Compounds for Restoring Anti-Tumor Immunity
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Solution Overview
Problem
Current therapies lack effective compounds capable of modulating CD73 activity, which is overexpressed in various cancers and contributes to immunosuppression and tumor growth, highlighting an unmet need for new CD73 inhibitors.
Innovation Solution
Development of novel organic compounds that can modulate CD73 activity, including pharmaceutically acceptable salts, solvates, tautomers, stereoisomers, and deuterated analogs, which are designed to target and inhibit CD73, thereby enhancing anti-tumor immunity.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current therapies are used, then treatment is provided for cancer patients, but they lack effective compounds capable of modulating CD73 activity
Solution Approach 1:
The patent segments the therapeutic approach by developing a series of compounds with different structural modifications (various R groups, linkers, and heterocyclic moieties) to target CD73. This segmentation allows exploration of structure-activity relationships to identify effective CD73 modulators when no such compounds were previously available.
Solution Approach 2:
The patent applies parameter changes by systematically varying chemical parameters of the compounds (molecular weight, lipophilicity, hydrogen bonding capacity, steric properties) to optimize CD73 modulation. The compounds of Formula I and its variants enable tuning of pharmacological parameters to achieve reliable CD73 inhibition.
2Object-affected harmful factors
If CD73 is overexpressed in cancer, then tumor growth is promoted through immunosuppression, but effective inhibition compounds are lacking
Solution Approach 1:
The patent introduces compounds of Formula I as intermediary substances that mediate between the immune system and tumor cells by inhibiting CD73. These compounds serve as chemical mediators that block the conversion of AMP to adenosine, thereby preventing the immunosuppressive signaling pathway that promotes tumor growth.
Solution Approach 2:
The patent converts the harmful overexpression of CD73 into a therapeutic target. By designing compounds that specifically inhibit CD73, the patent transforms the pathological condition (CD73 overexpression causing immunosuppression) into an opportunity for targeted therapy, where inhibiting the enzyme reverses the harmful effects and restores anti-tumor immunity.
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
These compounds enhance anti-tumor immune responses by inhibiting CD73, potentially improving treatment outcomes for various cancers and other conditions associated with CD73 overexpression.
Implementation Method 1
CD73, a highly conserved ecto-nucleotidase, is a dimeric enzyme that is expressed on the outer leaflet of the plasma membrane. It catalyzes the dephosphorylation of a subset of 5′ nucleotides, among which 5′-adenosine monophosphates (AMP) is the primary substrate. The adenosine is produced by CD73 catalyzed AMP hydrolysis
Data Source
AI summary
Disclosed are compounds capable of modulating CD73, of Formula I:or a pharmaceutically acceptable salt, a solvate, a tautomer, a stereoisomer or a deuterated analog thereof, wherein R1, R2, R3, A, L, and G are as described in any of the embodiments described in this disclosure; compositions thereof; and uses thereof.