CKRD Peptides Modulate Chemokine Networks for Inflammatory Disease
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Solution Overview
Problem
Current drug discovery strategies, focusing on single target drugs, are inadequate for multi-factorial diseases like diabetes, cancer, and arthritis due to their inability to effectively modulate complex protein networks, leading to inefficacy and side effects, particularly in detecting low affinity protein-protein interactions which are crucial for multi-target therapies.
Innovation Solution
Development of CK Receptor-Derived (CKRD) peptides and peptidic compounds that modulate immune system activity by interacting with chemokines and their receptors, specifically designed to be low affinity and transient, allowing for the modulation of multiple disease-related chemokines and receptors.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If single target drugs are used to treat multi-factorial diseases, then drug specificity is improved, but therapeutic efficacy deteriorates
Solution Approach 1:
The patent applies multi-functionality by designing a single drug molecule that can simultaneously target multiple disease-related proteins within the chemokine network. This allows the drug to address multiple pathogenic factors in multi-factorial diseases like arthritis, diabetes, and cancer, thereby improving therapeutic efficacy while maintaining reasonable specificity through selective modulation of disease-associated proteins
2Reliability
If high affinity binding drugs are used, then drug potency is improved, but detection of weak interactions deteriorates
Solution Approach 1:
The patent applies parameter changes by deliberately selecting drugs with low affinity (Kd≥μM) and rapid kinetic (1-100 s−1) binding characteristics. This parameter optimization enables the drugs to act as transient binding agents that can modulate multiple targets simultaneously, while also making them detectable through appropriate screening methods that can capture weak but biologically significant interactions
3Productivity
If High Through-put Screening is used to identify drug leads, then screening efficiency is improved, but detection of weakly binding compounds deteriorates
Solution Approach 1:
The patent applies the intermediary principle by introducing a mediator substance that enhances the detectability of weakly binding compounds during HTS. This mediator allows low affinity interactions to be amplified or stabilized during screening, enabling their detection despite the low concentration (≤μM) conditions used in high-throughput formats, thus reconciling screening efficiency with detection sensitivity
Data Source
AI summary
The invention provides pharmaceutical compositions comprising at least a portion of a chemokine receptor or a G-protein coupled receptor. The pharmaceutical composition of the invention may be used for altering immune system functioning, for example, to treat an immune system disorder, such as an autoimmune disease, multiple sclerosis, transplant rejection, psoriasis, rheumatoid arthritis and asthma. The invention also provides peptides that may be used individually, in combination with, or in combination with other therapeutic agents such as steroid, non-steroid anti-inflammatory drug, immune modulator or immune suppressor.