Selective Sigma-2 Ligands for TMEM97 Neuroprotective Modulation
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Solution Overview
Problem
Current treatments for neurological disorders and neurodegenerative diseases, such as Huntington's disease (HD), lack effective modulators for the sigma 2 receptor (σ2R/TMEM97), which are implicated in various disease contexts including cancer, neuropathic pain, traumatic brain injury, alcohol use disorder, and Alzheimer's disease.
Innovation Solution
Development of compounds that modulate the activity of the sigma 2 receptor (σ2R/TMEM97), specifically targeting transmembrane protein 97 (TMEM97), with specific chemical structures defined by varying substituents and linkages, to potentially provide neuroprotective effects.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing treatments for neurological disorders are used, then current therapeutic options are available, but effective modulators for sigma 2 receptor (σ2R/TMEM97) are lacking
Solution Approach 1:
The patent modifies the chemical structure of sigma 2 receptor ligands by changing molecular parameters (substituents, linkages, stereochemistry) to create compounds with improved pharmacological properties. This includes modifying affinity, selectivity, and functional activity at the σ2R/TMEM97 receptor to achieve effective modulation for neurological disorders.
Solution Approach 2:
The invention creates composite molecular structures by combining different pharmacological fragments and functional groups into unified compound molecules. These composite structures integrate multiple functional elements to achieve both high affinity binding and selective modulation of σ2R/TMEM97 signaling pathways.
2Reliability
If compounds are developed to modulate σ2R/TMEM97, then neuroprotective effects are achieved, but the complexity of chemical structures increases
Solution Approach 1:
The patent divides the complex molecular structure into distinct functional segments: pharmacophore core, substituent groups, and linkage regions. Each segment contributes specific pharmacological properties, allowing systematic optimization of neuroprotective activity while managing overall structural complexity through modular design.
Solution Approach 2:
The invention applies different chemical properties to specific regions of the molecule. Certain substituents are positioned at locations where they provide specific functional effects (e.g., affinity enhancement, selectivity, or metabolic stability), optimizing the balance between neuroprotective efficacy and structural manageability.
3Measurement precision
If selective sigma 2 receptor ligands are developed, then therapeutic specificity is improved, but the body of knowledge about σ2R function remains limited
Solution Approach 1:
The patent compounds serve as intermediary tools that bridge the gap between limited basic science knowledge and therapeutic application. By designing ligands with defined pharmacological profiles, these compounds enable systematic investigation of σ2R/TMEM97 function in disease models while providing selective modulation for treatment development.
Data Source
AI summary
The present disclosure relates to compounds that may be used to modulate the activity of a σ2R/TMEM97 receptor. The compounds may be further defined by the formula: (IA), (IB), or (IC) wherein the variables are as described herein. The present disclosure also provides pharmaceutical compositions of the compounds. Also, provided herein are methods of using the compounds in the treatment of neurodegenerative diseases or disorders among other indications.