PLXDC-Targeting Compounds for Existing Pathogenic Blood Vessels
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Solution Overview
Problem
Current anti-angiogenic therapies target only newly formed blood vessels, failing to address existing blood vessels contributing to disease progression, leading to drug resistance, invasion, and metastasis, and are ineffective in treating pathogenic blood vessel disorders such as cancer and other angiogenesis-related conditions.
Innovation Solution
Development of compounds that modulate PLXDC1 and/or PLXDC2 proteins, inducing NFκB activation and necrosis in pathogenic blood vessels, specifically targeting and killing existing blood vessels associated with disorders like cancer and diabetic retinopathy.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current anti-angiogenic therapies are used to target newly formed blood vessels, then tumor growth can be inhibited, but existing blood vessels contributing to disease progression are not treated, leading to drug resistance and incomplete treatment
Solution Approach 1:
The therapy is segmented into two distinct components: (1) anti-angiogenic agents that target newly formed blood vessels, and (2) compounds that target existing pathogenic blood vessels. This segmentation allows each component to address specific subsets of the problem without interfering with the other, achieving comprehensive coverage of both new and existing vessels.
Solution Approach 2:
The patent develops compounds with universal applicability that can target both newly formed and existing blood vessels across multiple disease contexts (cancer, retinopathy, AMD). The compounds act on endothelial cells in existing vessels while sparing healthy vessels, providing a multi-functional solution that addresses the limitations of previous single-target therapies.
2Ease of manufacture
If anti-angiogenic therapies target only newly formed blood vessels, then drug development is simpler, but disease progression is worsened due to untreated existing blood vessels
Solution Approach 1:
The therapeutic approach is divided into two separate drug development programs: one for anti-angiogenic agents targeting new vessels, and another for compounds targeting existing vessels. This segmentation maintains the relative simplicity of developing each individual agent while achieving comprehensive disease treatment through combination therapy.
Solution Approach 2:
The patent uses disease-specific markers and imaging techniques as intermediaries to identify and select patients who will benefit from the dual-targeting approach. These intermediaries bridge the gap between the simplified single-target therapies and the complex multi-target treatment outcome by enabling precise patient stratification.
3Productivity
If compounds target existing blood vessels to induce necrosis, then tumor shrinkage is achieved, but healthy vessels may be affected
Solution Approach 1:
The compounds exhibit local quality by selectively inducing necrosis in pathogenic blood vessels while sparing healthy vessels. This selectivity is achieved through targeting specific molecular markers or physiological characteristics that distinguish diseased vessels from healthy ones, allowing tumor shrinkage without damaging normal tissue.
Solution Approach 2:
The therapy applies partial action by inducing necrosis only in the subset of blood vessels that are pathogenic (existing vessels supporting tumors), rather than affecting all blood vessels. This controlled partial destruction achieves tumor shrinkage while preserving the majority of healthy vasculature.
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
The compounds effectively induce necrosis in pathogenic blood vessels, reducing tumor size and suppressing abnormal angiogenesis without affecting healthy vessels, offering a complementary therapy to anti-angiogenic treatments.
Implementation Method 1
the compound induces NFκB activation in pathogenic blood vessels. In some embodiments, the compound increases necrosis of pathogenic blood vessels
Data Source
AI summary
The disclosure provides compounds, and compositions, including pharmaceutical compositions, kits that include the compounds, and methods of using (or administering) and making the compounds. The disclosure further provides compounds or compositions thereof for use in a method of modulating PLXDC1 (TEM7) and/or PLXDC2 or killing pathogenic blood vessels. The disclosure further provides compounds or compositions thereof for use in a method of treating a disease, disorder, or condition that is mediated, at least in part, by PEDF receptors or by angiogenesis.