LANCL2-Mediated PPARγ Activation for Safer Antidiabetic Therapy
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Solution Overview
Problem
Current antidiabetic and anti-inflammatory medications have significant side effects, and there is a need for novel, safer therapeutic agents that can effectively manage blood glucose levels and treat chronic inflammatory and infectious diseases.
Innovation Solution
The use of lanthionine synthetase component C-like (LANCL) proteins as therapeutic targets for novel classes of anti-inflammatory, immune regulatory, and antidiabetic drugs, including abscisic acid (ABA) and its analogs, benzimidazophenyls, and other compounds that activate peroxisome proliferator-activated receptors (PPAR) through an alternative mechanism involving LANCL2 or other membrane proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current antidiabetic medications (sulfonylureas, Biguanides, TZDs) are used to manage blood glucose levels, then insulin-sensitizing effects are achieved, but serious side effects occur including hypoglycemia, gastrointestinal issues, liver damage, fluid retention, and weight gain
Solution Approach 1:
The patent introduces LANCL2 as an intermediary protein that mediates the action of PPARγ agonists. Instead of drugs directly activating PPARγ, they first bind to LANCL2, which then facilitates PPARγ activation. This intermediary mechanism allows for more controlled and selective drug action, potentially reducing off-target side effects while maintaining therapeutic efficacy for blood glucose management
Solution Approach 2:
The patent explores changing the mechanism of action parameter by discovering that PPARγ agonists can act through two different pathways: direct PPARγ binding or LANCL2-mediated binding. This parameter change enables the development of drugs with improved safety profiles by selecting the LANCL2-mediated pathway that avoids direct PPARγ activation and its associated side effects
2Reliability
If current anti-inflammatory medications (NSAIDs) are used to treat inflammatory diseases, then anti-inflammatory effects are achieved, but significant side effects occur including immune suppression that increases risk of cancer and infections
Solution Approach 1:
LANCL2 serves as a selective intermediary that enables anti-inflammatory drug action through a different pathway than traditional NSAIDs. By targeting the LANCL2-PPARγ axis, the patent aims to achieve anti-inflammatory effects without the immune suppression mechanism that characterizes NSAID therapy, thereby reducing cancer and infection risks
Solution Approach 2:
The patent extracts the inflammatory pathway control from the broad immune suppression mechanism of NSAIDs. By specifically targeting LANCL2 and the PPARγ pathway, the invention isolates anti-inflammatory effects from the harmful immune suppression side effects, achieving selective inflammation control without systemic immune compromise
3Reliability
If TZD drugs (such as Avandia) are used for diabetes treatment, then insulin-sensitizing effects are achieved, but increased risk of heart attack and liver damage occurs leading to market restrictions
Solution Approach 1:
The patent introduces LANCL2 as a protective intermediary layer between TZD-like drugs and their targets. By requiring LANCL2 mediation for drug action, the system enables insulin-sensitizing effects while filtering out the toxic effects that directly damage cardiovascular and hepatic systems, as demonstrated by the superior safety profile of ABA compared to traditional TZDs
Data Source
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AI summary
The present invention relates to the field of medical treatments for diseases and disorders. More specifically, the present invention relates to the use of the lanthionine synthetase component C-like (LANCL) proteins as therapeutic targets for novel classes of anti-inflammatory, immune regulatory and antidiabetic drugs. This includes but it is not limited to abscisic acid (ABA), ABA analogs, benzimidazophenyls, repurposed drugs or drug combinations, including thiazolidinediones (TZDs); naturally occurring compounds such as conjugated diene fatty acids, conjugated triene fatty acids, isoprenoids, and natural and synthetic agonists of peroxisome proliferator- activated receptors that activate this receptor through an alternative mechanism of action involving LANCL2 or other membrane proteins to treat or prevent the common inflammatory pathogenesis underlying type 2 diabetes, atherosclerosis, cancer, some inflammatory infectious diseases such as influenza and autoimmune diseases including but not limited to inflammatory bowel disease (Crohn's disease and Ulcerative colitis), rheumatoid arthritis, multiple sclerosis and type 1 diabetes and other chronic inflammatory conditions.