SorCS2 Lipidated Cyclic Peptides for Brain Availability
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Solution Overview
Problem
Current modulators of the SorCS2 pathway are not conveniently manufactured, lack high potency and selectivity, and have undesirable pharmacokinetic parameters, such as low brain availability and high clearance rates, limiting their therapeutic efficacy in treating neurodegenerative diseases.
Innovation Solution
Development of lipidated and cyclic peptides with specific sequences, such as (SEQ ID No. 51)X2-X3-E-H-X4-E, where X2, X3, and X4 represent specific amino acids or their conservatively substituted variants, which modulate the SorCS2 pathway to enhance neurotrophic signaling and clear misfolded proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Ease of manufacture
If current modulators of the SorCS2 pathway are used, then some therapeutic effect is achieved, but they are not conveniently manufactured and have undesirable pharmacokinetic parameters
Solution Approach 1:
The patent modifies the molecular structure of peptide modulators by changing parameters such as incorporating cyclic structures, adding lipidations, and optimizing amino acid sequences. These parameter changes improve both manufacturability and pharmacokinetic properties including brain availability and clearance rates, resolving the technical contradiction between ease of manufacture and reliability of pharmacokinetic parameters
2Reliability
If current modulators of the SorCS2 pathway are used, then some therapeutic effect is achieved, but they have low brain availability and high clearance rates
Solution Approach 1:
The patent applies parameter changes by modifying the chemical structure of the peptides through cyclic formation and lipidation. These modifications reduce clearance rates and improve brain availability, thereby enhancing therapeutic efficacy while minimizing substance loss through rapid clearance
Solution Approach 2:
The patent creates composite molecular structures by combining peptide sequences with cyclic configurations and lipid moieties. This composite approach produces modulators that simultaneously achieve therapeutic efficacy and improved pharmacokinetic profiles with lower clearance rates
Data Source
AI summary
SorCS2 related lipidated cyclic peptides, cyclic peptides, lipidated linear peptides, linear peptides which may be of use in medicine, and related aspects.