Modulating Aiolos and Ikaros Proteins to Restore Homeostasis
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Solution Overview
Problem
Current treatments for inflammatory and cancer-related disorders often face challenges due to protein malfunction, including overexpression, underexpression, or misregulation, leading to side effects and limited therapeutic efficacy, particularly with systemic delivery of cytokines like IL-2, and there is a need for compounds that can modulate protein function to restore homeostasis.
Innovation Solution
The development of compounds of Formula (I), which can modulate protein levels to restore protein homeostasis, inhibit cytokine activity, and target proteins such as Aiolos and ikaros, thereby treating conditions associated with protein imbalance and malfunction, including inflammation and cancer.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If systemic delivery of cytokines like IL-2 is used to treat cancer, then therapeutic efficacy is improved, but side effects increase and tolerance decreases
Solution Approach 1:
The patent divides the systemic delivery approach into targeted local delivery systems. Specifically, it uses tumor-targeting nanoparticles and antibody-cytokine conjugates that segment the delivery mechanism to reach only tumor sites, thereby maintaining therapeutic efficacy while reducing systemic side effects.
Solution Approach 2:
The patent introduces intermediary molecules such as tumor-targeting antibodies and nanoparticle carriers that mediate between the cytokine therapy and the tumor. These intermediaries enable selective delivery of IL-2 to tumor cells while protecting healthy tissues from exposure, thus improving the therapeutic index.
2Reliability
If large amounts of IL-2 are injected to achieve therapeutic levels, then cancer treatment efficacy is improved, but autoimmune side effects increase
Solution Approach 1:
The patent applies local quality by creating high concentrations of IL-2 specifically at the tumor site through targeted delivery systems. The tumor-targeting nanoparticles and conjugates ensure that therapeutic levels are achieved locally without requiring large systemic doses, thereby preventing autoimmune reactions in healthy tissues.
Solution Approach 2:
The patent employs preliminary action by pre-targeting tumors with antibodies or targeting ligands before administering the cytokine. This preliminary step ensures that when IL-2 is delivered, it is already positioned at the tumor site, maximizing local efficacy while minimizing systemic exposure and autoimmune side effects.
3Reliability
If protein levels are modulated to restore homeostasis, then disease treatment is improved, but complexity of compound design increases
Solution Approach 1:
The patent applies universality by designing compounds that can modulate multiple protein targets involved in disease pathology. The small molecules are designed to restore protein homeostasis across different disease contexts by targeting conserved pathways, thereby simplifying the overall therapeutic approach while maintaining effectiveness.
Solution Approach 2:
The patent uses parameter changes by modifying physical and chemical properties of the compounds to optimize their ability to modulate protein levels. By adjusting parameters such as molecular size, hydrophobicity, and binding affinity, the patent achieves effective protein homeostasis restoration with relatively simple molecular structures.
Data Source
AI summary
The present invention provides modulators of protein function, to restore protein homeostasis, including cytokine, aiolos, and/or ikaros activity, and cell-cell adhesion. The invention provides methods of modulating protein-mediated diseases, such as cytokine-mediated diseases, disorders, conditions, or responses. Compositions, including in combination with other cytokine and inflammatory mediators, are provided. Methods of treatment, amelioration, or prevention of protein-mediated diseases, disorders, and conditions, such as cytokine-mediated diseases, disorders, and conditions, including inflammation, fibromyalgia, rheumatoid arthritis, osteoarthritis, ankylosing spondylitis, psoriasis, psoriatic arthritis, inflammatory bowel diseases, Crohn's disease, ulcerative colitis, uveitis, inflammatory lung diseases, chronic obstructive pulmonary disease, Alzheimer's disease, and cancer, are provided.