Peptide Borate Ester Compounds for Oral Proteasome Inhibition
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Solution Overview
Problem
Current anti-cancer drugs, such as bortezomib, are expensive and have significant side effects, necessitating the development of potent proteasome inhibitors with lower toxicity and cost for treating various cancers.
Innovation Solution
Synthesis of novel peptide borate ester compounds with proteasome inhibitory function, designed as 20S proteasome inhibitors that can be taken orally, effectively blocking tumor cell proliferation and inducing apoptosis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If bortezomib is used as an anti-cancer drug, then proteasome inhibition efficacy is improved, but drug cost and side effects increase
Solution Approach 1:
The patent modifies the chemical structure parameters of bortezomib by replacing the boronic acid group with a borate ester group, creating novel compounds with improved pharmacokinetic properties. This structural parameter change maintains proteasome inhibition efficacy while reducing toxicity and enabling oral administration, directly addressing the contradiction between efficacy and harmful effects
Solution Approach 2:
The invention creates composite molecular structures by combining peptide sequences with borate ester moieties, forming hybrid compounds that exhibit both proteasome inhibition activity and improved drug-like properties. These composite structures achieve the desired balance between therapeutic efficacy and reduced side effects
2Ease of operation
If Velcade is administered subcutaneously, then patient tolerance and absorption are improved, but treatment complexity and cost increase
Solution Approach 1:
The patent changes the chemical parameters of the drug molecule by introducing borate ester groups, which fundamentally alter the pharmacokinetic properties. This enables the drug to be administered orally rather than requiring subcutaneous injection, simplifying the administration process while maintaining therapeutic efficacy and reducing treatment complexity
3Reliability
If peptide borate ester compounds are synthesized with novel structures, then proteasome inhibition activity is improved, but synthesis complexity increases
Solution Approach 1:
The synthesis approach divides the molecule into distinct segments: a peptide portion and a borate ester portion. These segments can be synthesized separately using established methodologies and then coupled together, reducing the overall synthesis complexity while maintaining the novel structure required for high proteasome inhibition activity
Solution Approach 2:
The patent employs peptide coupling reagents as intermediaries to facilitate the connection between the peptide sequence and the borate ester group. This intermediary approach enables modular synthesis, allowing each component to be optimized independently while simplifying the overall synthesis process
Data Source
Figure 1~2
AI summary
Provided are a peptide borate ester compound or a pharmaceutically acceptable salt thereof, a preparation method therefor, and pharmaceutical use thereof. The peptide borate ester compound or pharmaceutically acceptable salt thereof has a structure as shown in Formula (I), and is useful in the preparation of proteasome inhibitors to treat solid tumors and hematoma.