CSNK1D Inhibitors for Circadian Rhythm Normalization
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Solution Overview
Problem
Current treatments for mood disorders and circadian rhythm disruptions, such as major depressive disorder and seasonal affective disorder, are inadequate in addressing the underlying circadian disruptions, and existing therapies have limited efficacy in normalizing sleep-wake cycles and circadian rhythms.
Innovation Solution
Development of small molecule inhibitors targeting Casein kinase 1 delta (CSNK1D) to modulate circadian rhythms, which are administered as chemical entities in pharmaceutical compositions to treat various mood disorders, neurodegenerative disorders, and metabolic disorders by normalizing circadian disruptions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for mood disorders are used, then depression and anxiety symptoms are managed, but underlying circadian rhythm disruptions are not effectively addressed
Solution Approach 1:
The patent introduces CSNK1D inhibitors as intermediary compounds that mediate between the treatment goal and the underlying circadian disruption mechanism. These inhibitors specifically target the casein kinase 1 delta enzyme, which is a key regulator of circadian rhythms, thereby addressing the root cause rather than just symptoms
Solution Approach 2:
The invention changes the therapeutic parameter from general mood stabilization to specific circadian rhythm normalization by targeting CSNK1D enzyme activity. This parameter change enables more precise modulation of the circadian clock mechanism, directly addressing the underlying rhythm disruptions
2Ease of operation
If existing therapies are administered, then some mood disorder symptoms are alleviated, but sleep-wake cycles remain abnormal
Solution Approach 1:
The patent applies preliminary action by targeting the circadian clock mechanism before sleep-wake cycle disruptions fully manifest. By inhibiting CSNK1D, the treatment proactively normalizes the underlying circadian rhythm that governs sleep-wake cycles, preventing further disruption and promoting natural cycle restoration
3Quantity of substance
If conventional mood disorder treatments are used, then acute symptoms are reduced, but long-term circadian rhythm normalization is not achieved
Solution Approach 1:
The patent incorporates feedback mechanisms by targeting the circadian clock's self-regulating properties. CSNK1D inhibition allows the circadian system to naturally detect and correct its own rhythm disruptions through its inherent feedback loops, leading to sustained long-term normalization rather than temporary symptom relief
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 CSNK1D inhibitors effectively normalize circadian rhythms, reducing depression and anxiety-like behaviors, improving mood disorders, and exhibiting therapeutic benefits in treating a wide range of conditions including mood disorders, neurodegenerative diseases, and metabolic disorders.
Implementation Method 1
Casein kinase 1 delta (CSNK1D) is known to modulate the various feedback loops of the internal canonical circadian clock by phosphorylating PER2
Data Source
AI summary
A compound of Formula (I), pharmaceutical compositions containing them, methods of making them, and methods of using them including methods for treating disease states, disorders, and conditions associated with casein kinase 1 delta (CSNK1D) modulation, such as those associated with mood/psychiatric disorders, neurodegenerative diseases, cancers, addiction and substance abuse disorders, pain, and metabolic diseases.Wherein R1, R2, R3, and R4, are defined herein.