SDC-TRAP Conjugates for Targeted Cancer Therapy
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Solution Overview
Problem
Current chemotherapeutic treatments for cancer, such as those targeting heat shock proteins like Hsp90, face limitations due to undesired side effects and toxicity, and there is a need for therapeutic molecules that can selectively target overexpressed proteins in cancer cells while minimizing impact on normal cells.
Innovation Solution
Development of Small molecule Drug Conjugates (SDC-TRAPs) that consist of an effector moiety conjugated to a binding moiety, allowing for targeted delivery of cytotoxic agents to cancer cells by selectively binding to overexpressed proteins like Hsp90, enabling passive or active transport and controlled release of the effector moiety within the cells.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional chemotherapeutic treatments targeting Hsp90 are used, then therapeutic efficacy against cancer cells is improved, but systemic toxicity and undesired side effects increase
Solution Approach 1:
The therapeutic agent is segmented into two distinct components: a binding moiety that selectively targets Hsp90 in cancer cells and an effector moiety that delivers the cytotoxic effect. This segmentation allows the binding moiety to guide the effector moiety specifically to cancer cells, improving therapeutic efficacy while reducing systemic toxicity by limiting the distribution of the toxic component to target cells only.
Solution Approach 2:
The binding moiety acts as an intermediary that mediates between the effector moiety and the Hsp90 target. It selectively binds to Hsp90 in cancer cells and facilitates the delivery of the effector moiety to the target, thereby enabling precise targeting of the toxic effect to cancer cells while sparing normal cells from exposure.
2Productivity
If conventional chemotherapeutic treatments are used, then cancer cell killing is achieved, but selectivity between cancer cells and normal cells deteriorates
Solution Approach 1:
The binding moiety is designed with specific molecular characteristics that confer selective affinity for Hsp90 in cancer cells versus normal cells. This local quality difference in binding affinity enables the conjugate to preferentially accumulate in and act upon cancer cells, achieving both high cancer cell killing and improved selectivity simultaneously.
3Reliability
If high doses of cytotoxic agents are administered, then therapeutic efficacy is improved, but toxicity to normal cells increases
Solution Approach 1:
By segmenting the therapeutic into a binding moiety and effector moiety, the effector moiety can be administered at doses sufficient to achieve therapeutic efficacy in cancer cells, while the binding moiety ensures selective delivery to cancer cells, thereby preventing proportional toxicity to normal cells that would occur with conventional uniform dosing.
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 facilitate the delivery of toxic compounds to cancer cells at sub-toxic levels, reducing systemic toxicity and enhancing therapeutic efficacy while prolonging the presence of the effector moiety in target cells, thereby improving treatment outcomes with reduced side effects.
Implementation Method 1
a binding moiety, which may be an Hsp90 binding moiety
Implementation Method 2
SDC-TRAPs facilitate the delivery of toxic compounds to cancer cells
Implementation Method 3
allowing for targeted delivery of cytotoxic agents to cancer cells by selectively binding to overexpressed proteins like Hsp90, enabling passive or active transport
Implementation Method 4
enabling passive or active transport and controlled release of the effector moiety within the cells
Data Source
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.