Antrodia Camphorata Compounds as FGF21 Agonists
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Solution Overview
Problem
Current FGF21 and RDH10 agonists, particularly FGF21 analogues, face challenges such as high effective doses due to potential resistance, poor pharmacokinetic properties, and side effects like osteoporosis and severe pruritus. Additionally, there is a lack of effective small molecule agonists for FGF21, and existing compounds like obeticholic acid have weak upregulation effects and significant side effects.
Innovation Solution
The use of specific chemical components and extracts from the natural fungus Antrodia camphorata, such as Antcin K, Antcin C, and their derivatives, which exhibit significant FGF21 agonistic and/or RDH10 agonistic effects. These compounds can be used to prepare FGF21 agonists and/or RDH10 agonists for the treatment or prevention of lipid metabolism disorders and related diseases like non-alcoholic steatohepatitis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If FGF21 analogues (macromolecules or polypeptides) are used to treat lipid metabolism disorders, then FGF21 agonistic activity is achieved, but pharmacokinetic properties deteriorate (low half-life, poor oral bioavailability) and administration complexity increases (injection required)
Solution Approach 1:
The patent changes the molecular parameter from macromolecular polypeptide to small molecule compound, fundamentally altering pharmacokinetic properties while maintaining FGF21 agonistic activity through structural optimization and molecular design
Solution Approach 2:
The patent creates small molecule copies that mimic the biological activity of FGF21 polypeptide without replicating its macromolecular structure, achieving similar therapeutic effects with improved pharmacokinetic properties
2Reliability
If FGF21 analogues are used at high effective doses to overcome resistance, then therapeutic efficacy is maintained, but harmful side effects increase (bone loss, osteoporosis, inhibition of growth hormone axis)
Solution Approach 1:
The patent optimizes the dosage parameter by using small molecule compounds that achieve therapeutic efficacy at lower doses compared to FGF21 analogues, thereby reducing the threshold for harmful side effects
Solution Approach 2:
The patent employs small molecule compounds with favorable pharmacokinetic profiles that achieve sustained therapeutic effects without the accumulation and long-term side effects associated with high-dose polypeptide administration
3Quantity of substance
If obeticholic acid is used to upregulate FGF21, then FGF21 levels increase, but upregulation effectiveness is weak and harmful side effects occur (severe pruritus)
Solution Approach 1:
The patent uses small molecule compounds as direct agonists of FGF21 and RDH10, acting as intermediaries that directly activate the target receptors rather than indirectly upregulating FGF21 expression, thereby achieving more effective and controllable therapeutic effects
Solution Approach 2:
The patent employs compounds that simultaneously act as both FGF21 agonists and RDH10 agonists, providing multi-functional therapeutic effects that address lipid metabolism disorders through multiple pathways while maintaining favorable safety profiles
Data Source
AI summary
The present invention relates to a use of a compound and an extract derived from natural fungus Antrodia camphorata in the preparation of an FGF21 agonist and/or an RDH10 agonist.