CBP/catenin antagonists modulating stem cell division
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Solution Overview
Problem
Current methods fail to effectively modulate symmetric versus asymmetric stem cell division, which is crucial for treating aging and aging-related conditions, and cancer stem cells exhibit aberrant regulation of these divisions leading to neoplastic proliferation.
Innovation Solution
CBP/β-catenin antagonists, such as ICG-001, are used to regulate human endogenous stem cells by modulating the balance between CBP-mediated and p300-mediated catenin transcription, influencing stem cell division modes to treat aging and cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current methods are used to treat aging and cancer, then general therapeutic approaches are applied, but they fail to effectively modulate symmetric versus asymmetric stem cell division
Solution Approach 1:
The patent segments the broad category of stem cell division into two distinct modes: symmetric division and asymmetric division. By developing compounds that selectively modulate one mode over the other, the invention enables targeted therapeutic intervention. Specifically, the compounds promote asymmetric division in somatic stem cells to treat aging while forcing symmetric division in cancer stem cells to induce differentiation, thereby resolving the contradiction between general effectiveness and specific adaptability.
2Reliability
If CBP/catenin antagonists are used to increase asymmetric divisions in somatic stem cells, then aging-related conditions are treated, but cancer stem cells must be forced to differentiate
Solution Approach 1:
The patent applies inversion by reversing the division mode requirement for cancer stem cells compared to normal somatic stem cells. While somatic stem cells are encouraged to undergo asymmetric division to treat aging, cancer stem cells are forced to undergo symmetric division to induce differentiation and eliminate their malignant properties. This inverted approach allows the same compound to treat both aging and cancer through opposite mechanistic actions.
3Adaptability or versatility
If standard therapies are applied to cancer stem cells, then general cancer treatment is provided, but the cells exhibit aberrant regulation leading to neoplastic proliferation
Solution Approach 1:
The patent introduces CBP/catenin antagonists as intermediary compounds that mediate the therapeutic effect by specifically targeting the aberrant stem cell division regulation in cancer. These compounds act as intermediaries between the administered drug and the cancer stem cells, forcing them to undergo symmetric division and differentiate, thereby overcoming the resistance to standard therapies and treating neoplastic proliferation effectively.
Data Source
AI summary
Provided are: composition and methods for: treating aging or an age-related condition, symptom or disease; stimulating hair growth, regrowth or pigmentation (or preventing hair loss); for increasing adenosine receptor expression in dermal cells (in combination with hair growth); for treating a condition or disease of the skin or at least one symptom thereof, including cosmetic treatment (e.g., wrinkles, hyperpigmentation, redness, rosacea, dryness, cracking, loss of firmness, loss of elasticity, thinning, and loss of vibrancy). The methods comprise administering a sufficient amount of the disclosed CBP/catenin (e.g., CBP/(β-catenin) antagonist compositions, and particularly wherein administration is in an amount and manner sufficient to provide for increasing the number of asymmetric renewing divisions relative to, or at the expense of symmetric divisions in relevant somatic stem cell population. In particular aspects, the CBP/catenin (e.g., CBP/(β-catenin) antagonist comprises an alkyl and/or fatty acid ester derivative of formula (I) as disclosed herein