Khoá luận tốt nghiệp: Nghiên cứu sàng lọc ảo các chất có khả năng gắn kết chọn lọc trên CXCR2 so với CXCR1

CXCR1/2, a pair of chemokine receptors, play a pivotal role in the human immune system and are implicated in a wide range of pathological conditions, including chronic obstructive pulmonary disease (COPD), asthma, cystic fibrosis, and various inflammatory and autoimmune diseases. The modulation of CXCR1/2 expression has shown therapeutic promise by attenuating inflammatory responses. Despite global in silico research on compounds targeting these receptors, and some small molecules reaching clinical trials, no drug has yet been approved for clinical use. Specifically, selective antagonism of CXCR2 is of great interest due to its broader affinity for ELR+ chemokines compared to CXCR1, suggesting a wider therapeutic window and fewer off-target effects. This study aims to address this critical gap by performing an in silico screening to identify novel small molecules with selective binding potential for CXCR2 over CXCR1.

Nghiên cứu viên trong lĩnh vực hóa dược, khám phá thuốc sử dụng máy tính, dược lý học, và sinh viên các ngành liên quan (dược học, hóa dược) quan tâm đến thụ thể chemokine và các bệnh viêm.

This academic thesis, titled "Nghiên cứu sàng lọc in silico các phân tử nhỏ có tiềm năng gắn kết chọn lọc trên CXCR2 so với CXCR1," systematically investigates the identification of selective CXCR2 antagonists using computational methods. Recognizing the crucial involvement of chemokine receptors CXCR1 and CXCR2 in numerous inflammatory and immune-mediated diseases, the study highlights the therapeutic advantage of selectively targeting CXCR2. The methodology employed a multi-faceted in silico approach, beginning with the collection of a comprehensive database of known CXCR2 antagonist compounds. Subsequently, detailed 3D-pharmacophore models were constructed based on this dataset, and 2D-QSAR models were developed using IC50 values of CXCR2 inhibitors to predict biological activity. Furthermore, CXCR2 homology models were built to characterize the receptor's structure, which is vital for molecular interaction studies. The core of the research involved docking simulations for both CXCR2 and CXCR1 to analyze binding interactions and compare binding scores, followed by an ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) evaluation to filter out compounds with unfavorable pharmacokinetic properties. Finally, a large-scale virtual screening was conducted on the ZINC database, a repository of commercially available compounds, to identify novel small molecules exhibiting selective binding to CXCR2. This research provides a robust framework for accelerating drug discovery by computationally prioritizing promising candidates, thereby reducing experimental time and costs. The findings hold significant implications for developing new therapeutic agents for a spectrum of conditions such as COPD, asthma, and inflammatory bowel diseases, by offering a selective approach that could enhance efficacy and minimize adverse effects associated with broad-spectrum chemokine receptor inhibition.