IBSG Webinar Tháng 8-2023: Khám Phá Thuốc cho Thụ Thể Adenosine A1

Kính mời quý độc giả tham dự buổi Webinar tháng 8-2023 do Nhóm Học Thuật Y Sinh IBSG tổ chức trực tuyến qua Zoom.

Trong buổi webinar chuyên đề này, IBSG hân hạnh được sự tham gia của:

TS Nguyễn T. Ngọc Anh: Research Fellow, Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Australia.

Để biết thêm chi tiết về diễn giả, xin mời quý độc giả xem các bài báo đã xuất bản tại Google Scholar:

https://scholar.google.com.au/citations?user=bbzCnZoAAAAJ&hl=en

Chủ đề: Advancing allosteric modulation to target the Adenosine A1 Receptor

Abstract:

The adenosine A1 G protein-coupled receptor (A1R) is an attractive therapeutic target for a range of cardiovascular and neuronal disorders. However, it remains sub-optimally targeted due to high doses and the lack of highly subtype-selective ligands causing adverse effects (such as bradycardia, atrioventricular block, and hypotension). Emerging paradigms of A1R pharmacology, including allostery and biased agonism, offer considerable clinical potential, presenting the opportunity to develop potent therapeutics with minimal on-target side effects. My research aims to understand the structural basis and the mechanism of allosteric modulation and biased agonism at the A1R and to develop a computational approach to identify novel A1R ligands. We have used a combined approach of mutagenesis, analytical pharmacology and molecular modelling (docking and molecular dynamics simulation) to identify molecular determinants of orthosteric ligand binding and activation, as well as allosteric modulation at the A1R. Subsequent structure-function studies validated the first high-resolution A1R structures in the inactive, active, allosteric modulator bound, and biased agonist bound conformations. Employing a high-throughput screening approach, we have elucidated the structure-activity relationship of a series of A1R-biased agonists, identifying a high potency A1R-biased agonist. We recently had three successful structure-based virtual ligand screening campaigns for novel orthosteric and allosteric ligands targeting A1R. Specifically, we discovered first-in-class A1R allosteric inhibitors, novel high-affinity A1R antagonists, and novel A1R allosteric enhancers. Currently, we are incorporating artificial intelligence deep learning models to assist our A1R drug discovery pipeline. Collectively, findings from my research will assist in overcoming the challenges associated with the discovery, validation, and development of novel A1R therapeutics with improved clinical efficacy for the treatment of major global health burdens.

Host: Nguyễn Bích Nụ

Thời gian: 9:00 – 10:00 sáng Chủ Nhật giờ Việt Nam, ngày 20.08.2023.

Zoom Meeting: 

https://uwmadison.zoom.us/j/92045899808?pwd=aWJsVzQ1Q092a1hwc2M3SkZxRkdLZz09

Meeting ID: 920 4589 9808

Passcode: IBSGW2023

Lưu ý: Khán giả không được quay phim hay chụp hình trong buổi thuyết trình vì diễn giả chia sẻ những kết quả chưa được công bố.