Allosteric Hemoglobin Modulators for Sickle Cell Polymerization
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Solution Overview
Problem
Current treatments for sickle cell disease, mediated by sickle hemoglobin (HbS), are inadequate, as existing allosteric modulators do not effectively address the disorder's underlying issues of abnormal hemoglobin leading to oxygen deficiency and vascular blockages.
Innovation Solution
Development of specific compounds and pharmaceutical compositions that act as allosteric modulators of hemoglobin, specifically designed to increase oxygen affinity and treat disorders associated with sickle cell anemia by modifying the structure and function of hemoglobin to prevent polymerization and improve cellular oxygenation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If existing allosteric modulators are used to treat sickle cell disease, then some therapeutic effect is achieved, but they do not effectively address the underlying issues of abnormal hemoglobin leading to oxygen deficiency and vascular blockages
Solution Approach 1:
The patent applies parameter changes by modifying the oxygen affinity of hemoglobin through allosteric modulation. The compounds change the physiological parameters of hemoglobin function, specifically increasing oxygen affinity to prevent polymerization of HbS and reduce sickling of red blood cells, thereby addressing the root causes of the disease
Solution Approach 2:
The patent uses small molecule compounds as intermediaries that bind to hemoglobin at allosteric sites. These intermediary molecules mediate the effect between the administered drug and the hemoglobin polymerization process, preventing the harmful polymerization without directly interfering with normal oxygen transport function
2Productivity
If hemoglobin binds and releases oxygen through conformational changes, then oxygen transport is achieved, but sickle hemoglobin becomes susceptible to polymerization causing sickle shape and vascular blockage
Solution Approach 1:
The patent applies preliminary anti-action by administering allosteric modulators that prevent the polymerization of sickle hemoglobin before it can occur. The compounds bind to hemoglobin in advance and stabilize it in a conformation that resists polymerization, thereby preventing the sickling process before it damages blood vessels
Solution Approach 2:
The invention changes the physical-chemical parameters of hemoglobin by introducing allosteric effectors that alter the polymerization propensity of HbS. The compounds modify the thermodynamic and kinetic parameters of hemoglobin behavior, increasing oxygen affinity and decreasing the tendency to polymerize under physiological conditions
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 compounds effectively increase oxygen affinity of hemoglobin S, thereby reducing the severity of sickle cell anemia symptoms by preventing polymerization and improving tissue oxygenation, offering a therapeutic approach to manage oxygen deficiency and related disorders.
Implementation Method 1
compounds and pharmaceutical compositions suitable as allosteric modulators of hemoglobin
Implementation Method 2
Hemoglobin binds and releases oxygen through conformational changes
Data Source
AI summary
Provide herein are compounds and pharmaceutical compositions suitable as modulators of hemoglobin, methods and intermediates for their preparation, and methods for their use in treating disorders mediated by hemoglobin and disorders that would benefit from tissue and/or cellular oxygenation.