ROR Modulators for Oral FGF21 Upregulation in Pancreatitis
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Solution Overview
Problem
There are no specific therapies for pancreatitis, a debilitating gastrointestinal disease, and existing treatments are supportive in nature, highlighting an unmet therapeutic need. Additionally, conditions like sarcopenia, stroke, and traumatic brain injury lack effective oral treatments, particularly for fibroblast growth factor 21 (FGF21)-deficient states.
Innovation Solution
Development of small molecule modulators of retinoic acid receptor-related orphan receptors (ROR) such as RORα, RORβ, or RORγ to increase endogenous FGF21 and miR122 levels, which can be administered orally to treat or prevent conditions associated with FGF21 deficiency, including pancreatitis, sarcopenia, stroke, and traumatic brain injury, and conditions associated with miR122, such as glioblastoma.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If small molecule modulators of ROR are developed to increase endogenous FGF21 levels, then therapeutic efficacy for pancreatitis and other FGF21-deficient conditions is improved, but the complexity of drug development and regulatory approval increases
Solution Approach 1:
The patent uses ROR modulators as intermediary compounds that indirectly increase FGF21 levels by modulating ROR bioactivity, rather than directly administering FGF21 or its analogs. This intermediary approach allows the drug to work through the body's natural regulatory pathways, potentially improving therapeutic efficacy while managing development complexity through a well-defined mechanism of action.
2Ease of operation
If oral administration of ROR modulators is used to treat pancreatitis and other conditions, then patient compliance and ease of administration are improved, but ensuring adequate bioavailability and reaching target tissues effectively becomes more challenging
Solution Approach 1:
The patent employs small molecule modulators with specific chemical structures designed to achieve optimal pharmacokinetic parameters for oral administration. By carefully adjusting molecular properties such as lipophilicity, molecular weight, and functional groups, the compounds can achieve adequate bioavailability and tissue penetration while maintaining oral administrability.
3Reliability
If FGF21 levels are increased to treat pancreatitis, then disease progression is slowed and severity is reduced, but the mechanisms underlying FGF21 deficiency and the optimal timing for intervention become more complex to determine
Solution Approach 1:
The patent leverages the feedback mechanism where ROR modulators increase endogenous FGF21 production through modulation of ROR bioactivity. This creates a self-regulating system where the body's own FGF21 levels are elevated in response to drug administration, and the effect can be monitored through FGF21 level measurements, providing both therapeutic action and a biomarker for disease management assessment.
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 ROR modulators effectively increase FGF21 and miR122 levels, treating, preventing, or reducing the severity of associated disorders by modulating ROR bioactivity, providing therapeutic benefits for pancreatitis, sarcopenia, stroke, traumatic brain injury, and glioblastoma.
Implementation Method 1
small molecule modulators of retinoic acid receptor-related orphan receptors (ROR) such as RORα, RORβ, or RORγ to increase endogenous FGF21 and miR122 levels
Data Source
AI summary
Compounds, compositions and methods for modulating retinoic acid receptor-like orphan receptors (ROR) so as to increase FGF21 levels, and treating and preventing disorders associated with FGF21, such as pancreatitis, sarcopenia, stroke, and traumatic brain injury, and to increase miR-122 levels, and treating and preventing disorders such as glioblastoma.