Modeling Cysteinyl Leukotriene Receptor Antagonist KNW for Possible Optimized Asthma Treatment
Abstract
Under-diagnosed and under-treated, particularly in low- and middle-income countries, asthma has affected 262 million people globally in 2019. Cysteinyl leukotriene receptors (Cys-LTRs) are a δ-branch of class A G protein-coupled receptors associated with physiological functions in airways with allergic inflammation. Current antiasthmatic medications such as pranlukast inhibit CysLT1R, yet many patients still do not respond to this drug. To better understand this process, the related receptor CysLT2R has been identified as a promising drug target for not only asthma but also other conditions such as brain injury and cancer. CysLT1R is associated with bronchoconstriction, inflammation, and mucus production in the airways of the lungs and bronchial tissues. When cysteinyl leukotrienes bind to CysLT1R, these effects are triggered contributing to the symptoms of asthma. CysLT2R functions are more diverse but are still involved in mediating inflammatory responses. While CysLT2R is expressed alongside CysLT1R on various immune cells, its specific functions have not been reported. Through the exploration and modeling of KNW (11a, a dual antagonist of CysLT1R and CysLT2R; PDB ID: 6RZ6), we gain further insight into the structural mechanisms of drug interactions with similar receptors responsible for mediating inflammation and bronchoconstrictive effects of cysteinyl leukotrienes. Enhancing the potency of dual antagonists holds the most potential to improve current treatments for severe atopic asthma.
Faculty Sponsors
Dr. Emily Schmitt Lavin, Dr. Arthur Sikora
Project Type
Event
Location
Alvin Sherman Library
Start Date
4-3-2024 12:30 PM
End Date
4-4-2024 1:30 PM
Modeling Cysteinyl Leukotriene Receptor Antagonist KNW for Possible Optimized Asthma Treatment
Alvin Sherman Library
Under-diagnosed and under-treated, particularly in low- and middle-income countries, asthma has affected 262 million people globally in 2019. Cysteinyl leukotriene receptors (Cys-LTRs) are a δ-branch of class A G protein-coupled receptors associated with physiological functions in airways with allergic inflammation. Current antiasthmatic medications such as pranlukast inhibit CysLT1R, yet many patients still do not respond to this drug. To better understand this process, the related receptor CysLT2R has been identified as a promising drug target for not only asthma but also other conditions such as brain injury and cancer. CysLT1R is associated with bronchoconstriction, inflammation, and mucus production in the airways of the lungs and bronchial tissues. When cysteinyl leukotrienes bind to CysLT1R, these effects are triggered contributing to the symptoms of asthma. CysLT2R functions are more diverse but are still involved in mediating inflammatory responses. While CysLT2R is expressed alongside CysLT1R on various immune cells, its specific functions have not been reported. Through the exploration and modeling of KNW (11a, a dual antagonist of CysLT1R and CysLT2R; PDB ID: 6RZ6), we gain further insight into the structural mechanisms of drug interactions with similar receptors responsible for mediating inflammation and bronchoconstrictive effects of cysteinyl leukotrienes. Enhancing the potency of dual antagonists holds the most potential to improve current treatments for severe atopic asthma.
