FAP-Targeting Cyclic Polypeptides for Tumor Retention
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Solution Overview
Problem
Current chemotherapy drugs lack specificity for targeting cancer-associated fibroblasts (CAFs) and exhibit low affinity and short retention at tumor sites, leading to ineffective therapeutic effects and side effects due to non-specific mechanisms.
Innovation Solution
A cyclic polypeptide compound designed to target FAP (fibroblast activation protein) expressed on CAFs, offering high tumor uptake and prolonged retention, suitable for clinical applications.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional chemotherapy drugs are used, then cancer treatment is achieved, but specificity for targeting cancer-associated fibroblasts is poor and side effects occur
Solution Approach 1:
The patent applies local quality by designing a cyclic polypeptide compound with specific amino acid sequences that are selectively recognized by FAP on CAFs. The compound structure includes specific residues (e.g., Tyr, Phe, Trp, His, Lys, Arg, Glu, Asp) arranged in a cyclic configuration that provides localized binding affinity for FAP, enabling targeted action on CAFs while sparing normal tissues, thus reducing side effects while maintaining treatment effectiveness.
2Reliability
If traditional chemotherapy drugs are used, then cancer treatment is achieved, but tumor site localization efficiency is low
Solution Approach 1:
The patent uses FAP as an intermediary target protein expressed on CAFs in the tumor microenvironment. The cyclic polypeptide compound acts as a ligand that binds to FAP, serving as a mediator to deliver therapeutic effects specifically to the tumor site. This intermediary approach enables efficient tumor site localization by exploiting the high expression of FAP on CAFs, which are key components of the tumor microenvironment, thereby improving localization efficiency compared to non-specific chemotherapy.
3Reliability
If small molecule ligands are used for targeted drugs, then tumor penetration and manufacturing cost are improved, but affinity for FAP is insufficient
Solution Approach 1:
The patent employs a composite approach by creating a cyclic polypeptide structure that combines multiple amino acid residues with specific functional properties. This cyclic polypeptide acts as a hybrid between small molecules and proteins, maintaining the favorable pharmacokinetic properties of small molecules (rapid penetration, lower cost) while achieving high affinity for FAP through the coordinated interaction of multiple amino acid side chains with the FAP binding site. The cyclic configuration provides structural stability and enhanced binding affinity.
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 cyclic polypeptide compound achieves enhanced tumor localization and stability, improving diagnostic accuracy and therapeutic efficacy by selectively binding to FAP, thereby addressing the limitations of existing treatments.
Implementation Method 1
The cyclic polypeptide compound achieves enhanced tumor localization and stability, improving diagnostic accuracy and therapeutic efficacy by selectively binding to FAP
Data Source
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AI summary
Provided are a cyclic polypeptide compound and the use thereof, and specifically disclosed are a cyclic polypeptide compound A and a cyclic polypeptide compound B. The cyclic polypeptide compound A is a compound formed by ion chelation of a compound X and a therapeutic radionuclide. The cyclic polypeptide compound B is a compound formed by ion chelation of a compound X and a diagnostic radionuclide. The compound can be used for diagnosis and treatment of FAP-related or mediated tumors, has high tumor uptake and long retention time, and has a wide application prospect.