SDC-TRAP Conjugates for Targeted Cancer Therapy
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Solution Overview
Problem
Current chemotherapeutic treatments for diseases like cancer are limited by undesired side effects due to non-specific targeting of therapeutic moieties, leading to poor prognosis and inefficacy.
Innovation Solution
Development of Small molecule Drug Congugates that are TRAPped intracellularly (SDC-TRAPs), which consist of an effector moiety conjugated to a binding moiety that selectively targets cells overexpressing specific proteins, such as Hsp90, using a cleavable bond to ensure intracellular retention and controlled release of the effector moiety.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If traditional chemotherapeutic agents are administered systemically, then they can reach target cells throughout the body, but they cause undesired side effects due to non-specific targeting of healthy cells
Solution Approach 1:
The chemotherapeutic agent is segmented into two functional components: a binding moiety that specifically recognizes and binds to overexpressed proteins on target cells, and an effector moiety that delivers the cytotoxic effect. This segmentation allows the binding moiety to guide the effector moiety specifically to target cells, reducing non-specific exposure of healthy cells and thereby minimizing side effects while maintaining therapeutic efficacy
Solution Approach 2:
The binding moiety acts as an intermediary that mediates between the effector moiety and the target cell. It specifically binds to overexpressed proteins on the surface of target cells, facilitating the selective delivery of the effector moiety to the intended target while preventing systemic exposure of healthy cells, thus resolving the contradiction between reaching target cells and avoiding side effects
2Productivity
If high doses of chemotherapeutic agents are used to improve treatment effectiveness, then therapeutic impact increases, but toxicity to healthy cells increases
Solution Approach 1:
By segmenting the chemotherapeutic agent into a binding moiety and an effector moiety, the system can achieve high therapeutic impact at lower overall doses. The binding moiety ensures concentrated delivery of the effector moiety to target cells, maximizing therapeutic impact locally without requiring high systemic doses that would cause widespread toxicity to healthy cells
Solution Approach 2:
The conjugate exhibits local quality by concentrating the cytotoxic effector moiety specifically at the target cell location through the binding moiety's selective recognition. This localized concentration achieves high therapeutic impact at the disease site while maintaining low systemic concentrations, thereby avoiding the need for high doses that would cause systemic toxicity
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
SDC-TRAPs enable targeted therapy with enhanced efficacy and reduced side effects by selectively delivering cytotoxic agents to cancer cells, maximizing the therapeutic impact while minimizing systemic toxicity.
Implementation Method 1
the effector moiety is conjugated via a cleavable bond or linker to the binding moiety, such that the cleavable bond or linker is preferentially cleaved after the SDC-TRAP enters the target cell
Implementation Method 2
certain SDC-TRAP molecules of the invention enter target cells by passive diffusion and are selectively retained in the target cells
Data Source
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AI summary
The present invention provides pharmacological compounds including an effector moiety conjugated to a binding moiety that directs the effector moiety to a biological target of interest. Likewise, the present invention provides compositions, kits, and methods (e.g., therapeutic, diagnostic, and imaging) including the compounds. The compounds can be described as a protein interacting binding moiety-drug conjugate (SDC-TRAP) compounds, which include a protein interacting binding moiety and an effector moiety. For example, in certain embodiments directed to treating cancer, the SDC-TRAP can include an Hsp90 inhibitor conjugated to a cytotoxic agent as the effector moiety.