Applying Computer- Aided Drug Discovery Techniques For the Improvement of Proton Pump Inhibitors Used For the Treatment of Eosinophilic Esophagitis (EoE)
Session Number
Project ID: CHEM 02
Advisor(s)
Dr. John Thurmond; Illinois Mathematics and Science Academy
Discipline
Chemistry
Start Date
19-4-2023 9:05 AM
End Date
19-4-2023 9:20 AM
Abstract
Eosinophilic Esophagitis (EoE) is an autoimmune condition that causes inflammation of the digestive tract due to a high buildup of eosinophils, a white blood cell that both mediates and controls responses to allergies and asthma. When trigger allergens are exposed to EoE patients, the immune system gets activated, leading to the buildup of eosinophils contributing to tissue damage and inflammation of the digestive tract. The most common class of medicines used to treat EoE are proton pump inhibitors (PPIs). This study tested Omeprazole, one of the first developed PPIs. This study also used the Aryl Hydrocarbon Receptor (AHR) as Omeprazole’s biological target protein. The AHR, once activated, mediates responses to both internal and external stimuli and aids in gene expression. Computer aided drug discovery programs were used to pinpoint the parts in omeprazole’s molecular structure that were not effectively binding to the AHR. Hundreds of novel structures were designed. Several of these novel structures have been recorded to have a significantly better binding affinity with the AHR than that of Omeprazole. These results have important implications that the use of computer aided drug design in the drug discovery process can aid in the development of treatments for Eosinophilic Esophagitis (EoE).
Applying Computer- Aided Drug Discovery Techniques For the Improvement of Proton Pump Inhibitors Used For the Treatment of Eosinophilic Esophagitis (EoE)
Eosinophilic Esophagitis (EoE) is an autoimmune condition that causes inflammation of the digestive tract due to a high buildup of eosinophils, a white blood cell that both mediates and controls responses to allergies and asthma. When trigger allergens are exposed to EoE patients, the immune system gets activated, leading to the buildup of eosinophils contributing to tissue damage and inflammation of the digestive tract. The most common class of medicines used to treat EoE are proton pump inhibitors (PPIs). This study tested Omeprazole, one of the first developed PPIs. This study also used the Aryl Hydrocarbon Receptor (AHR) as Omeprazole’s biological target protein. The AHR, once activated, mediates responses to both internal and external stimuli and aids in gene expression. Computer aided drug discovery programs were used to pinpoint the parts in omeprazole’s molecular structure that were not effectively binding to the AHR. Hundreds of novel structures were designed. Several of these novel structures have been recorded to have a significantly better binding affinity with the AHR than that of Omeprazole. These results have important implications that the use of computer aided drug design in the drug discovery process can aid in the development of treatments for Eosinophilic Esophagitis (EoE).