Antibody-Multidrug Conjugate Precursor with Branched Linker
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Solution Overview
Problem
Current antibody-drug conjugates (ADCs) face challenges in delivering multiple antitumor drugs effectively to cancer cells, leading to reduced efficacy and stability in blood circulation.
Innovation Solution
Development of an antibody-multidrug conjugate (AMDC) with a branched linker modified with lactonyl and phosphoryl groups, allowing for the conjugation of multiple antitumor drugs to an antibody, enhancing stability and pharmacokinetics.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If multiple antitumor drugs are conjugated to an antibody via a linker, then antitumor efficacy is improved, but stability in blood circulation deteriorates
Solution Approach 1:
The invention divides the single-linker structure into multiple separate linkers, each conjugating a different antitumor drug to the antibody. This segmentation allows each linker-drug combination to be optimized independently for both stability and efficacy, resolving the contradiction between maintaining blood circulation stability and achieving multiple drug delivery.
Solution Approach 2:
The invention changes the chemical parameters of the linker molecules by selecting from different linker types (e.g., cleavable linkers vs. non-cleavable linkers, different spacer lengths, different chemical compositions) to optimize the balance between blood circulation stability and drug release efficiency at the target site.
2Productivity
If a single antibody is used to deliver multiple drugs, then treatment efficiency is improved, but drug delivery precision deteriorates
Solution Approach 1:
The invention segments the drug delivery system by assigning different linkers with specific cleavage characteristics to different drugs, allowing each drug to be released under slightly different conditions or at different rates, thereby maintaining precision while delivering multiple therapies.
Solution Approach 2:
Different regions of the antibody-conjugate structure are assigned different properties through the use of diverse linkers with varying stability, cleavage mechanisms, and release kinetics, enabling localized optimization of drug delivery precision for each drug while maintaining overall treatment efficiency.
Data Source
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AI summary
Provided is a conjugate precursor for obtaining a more useful antitumor drug by further advancing a conventional antibody-drug conjugate. An antibody-multidrug conjugate precursor is represented by General Formula (I) below: [in the formula, symbols have the meanings described in the specification], or a salt thereof, and a synthetic intermediate thereof or a salt thereof.