HPTP-β Inhibitor Stabilizes Vasculature During IL-2 Therapy
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Solution Overview
Problem
Current treatments for vascular leak syndrome, often caused by infections or anticancer therapies, lead to complications such as sepsis and pulmonary edema, necessitating the development of methods to stabilize vascular integrity and prevent excessive vascular leakage.
Innovation Solution
Inhibiting the intracellular catalytic site of human protein tyrosine phosphatase beta (HPTP-β) in vascular endothelial cells, which reduces the dephosphorylation of the Tie-2 receptor tyrosine kinase, amplifying the Angiopoietin 1 signal and counteracting Angiopoietin 2's effects, thereby stabilizing the vasculature.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If Interleukin-2 is administered to boost immune system in malignant renal carcinoma patients, then immune system is enhanced, but vascular leak syndrome occurs causing treatment cessation
Solution Approach 1:
The patent applies preliminary anti-action by administering a Tie-2 signal amplifier (such as a protein tyrosine phosphatase inhibitor) before or during IL-2 therapy to preemptively counteract the vascular leak syndrome that would otherwise be caused by IL-2 administration. This allows the full course of cancer treatment to be completed without treatment cessation.
2Stability of the object's composition
If Tie-2 signal is amplified to stabilize vasculature, then vascular leakage is reduced, but the mechanism requires specific molecular inhibition
Solution Approach 1:
The patent uses an intermediary substance (Tie-2 signal amplifier or protein tyrosine phosphatase inhibitor) to mediate between the administered IL-2 and the vascular endothelium. This intermediary amplifies the protective Tie-2 signal in response to IL-2, stabilizing vasculature through a defined molecular pathway involving HPTP-beta inhibition and Tie-2 receptor activation.
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
This approach effectively prevents vascular leakage, allowing for prolonged administration of anticancer therapies and reducing mortality and morbidity associated with vascular leak syndrome.
Implementation Method 1
Disclosed herein are compounds that inhibit the intracellular catalytic site of human protein tyrosine phosphatase beta (HPTP-β) molecule
Data Source
AI summary
Disclosed are methods for treating Vascular Leak Syndrome. Further disclosed are methods for treating vascular leakage due to inflammatory diseases, inter alia, sepsis, lupus, inflammatory bowel disease. Yet further disclosed are methods for treating renal cell carcinoma and melanoma. Still further disclosed are methods for reducing metastasis of malignant cells and/or preventing the proliferation of carcinoma cells via spreading due to vascular leakage.