Notch Signaling Enhancers for Squamous Cell Carcinoma Treatment
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Solution Overview
Problem
Existing Notch signaling enhancers for treating Notch-associated diseases, such as cancer, are limited and often have drawbacks, and there is a need for potent compounds that can effectively upregulate Notch signaling to treat cancers that are not responsive to Notch signaling inhibitors.
Innovation Solution
Development of a family of small molecules, including phenoxybenzoic acids and phenoxynicotinic acids, which enhance Notch signaling by activating the Notch pathway, potentially treating cancers like cutaneous and lung squamous cell carcinoma, head and neck cancer, neuroendocrine tumors, and carcinoid tumors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Adaptability or versatility
If Notch signaling inhibitors are used to treat cancer, then cancers dependent on Notch signaling activation (such as T-ALL, CML, CLL, MCL, breast cancer, pancreatic cancer, prostate cancer, melanoma, brain tumors, and colorectal cancer) can be targeted, but Notch-associated diseases requiring Notch signaling enhancement (such as squamous cell carcinoma, neuroendocrine tumors, and carcinoid tumors) cannot be treated
Solution Approach 1:
The patent inverts the conventional approach of inhibiting Notch signaling and instead develops compounds that enhance Notch signaling. This inversion allows treatment of cancers where Notch acts as a tumor suppressor (such as squamous cell carcinoma, neuroendocrine tumors, and carcinoid tumors) while providing an alternative therapeutic strategy for Notch-associated malignancies that are not responsive to inhibitors
2Reliability
If known Notch signaling enhancers (such as valproic acid, resveratrol, phenethyl isothiocyanate, and flavonoids) are used, then Notch signaling can be enhanced, but high concentrations are required and they show limited potency
Solution Approach 1:
The patent modifies the chemical parameters of known Notch signaling enhancers by developing novel compounds with optimized molecular structures. The compounds of formula (I) feature specific structural modifications including various substituent groups (R1, R2, R3, R4, R5, R6) that enhance binding affinity and potency, allowing effective Notch signaling enhancement at lower concentrations compared to known compounds like valproic acid and resveratrol
3Reliability
If activating Notch ligand-mimicking peptides (such as JAG-1 protein peptide fragment) are used to upregulate Notch signaling, then Notch signaling can be enhanced, but the tool is still in development and only available for research
Solution Approach 1:
The patent replaces complex peptide-based approaches (JAG-1 protein peptide fragments) with small molecule compounds of formula (I). These small molecules offer advantages in terms of stability, ease of synthesis, and potential for clinical development. The compounds achieve Notch signaling enhancement through small molecule-ligand receptor interaction, replacing the need for large peptide structures that are difficult to manufacture and stabilize for clinical use
Data Source
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AI summary
The present invention relates to the use for enhancing Notch signaling in an individual, of a compound showing the general formula (I) and/or a pharmaceutically acceptable salt or ester thereof, for the treatment of a disease selected from the group of dermatological disorders including atopic dermatitis, psoriasis, immune related disorders, cancer, squamous cell carcinoma, cutaneous and lung squamous cell carcinoma, head and neck cancer, non-melanoma skin cancer, basal cell carcinoma and actinic keratosis, neuroendocrine tumors, neuroendocrine small cell carcinoma and carcinoid tumors, thyroid carcinomas, muscular disorders muscular dystrophy and impaired regeneration capacity after injury; use in immunotherapy for cancer.