Exploiting the Achilles' heel of cancer through a structure-based drug-repurposing approach and experimental validation of top drugs using the TRAP assay.

 0 Người đánh giá. Xếp hạng trung bình 0

Tác giả: Madhu Chopra, Divpreet Kaur, Daman Saluja

Ngôn ngữ: eng

Ký hiệu phân loại:

Thông tin xuất bản: Netherlands : Molecular diversity , 2025

Mô tả vật lý:

Bộ sưu tập: NCBI

ID: 712008

Telomerase, a reverse transcriptase implicated in replicative immortality of cancers, remains a challenging target for therapeutic intervention due to its structural complexity and the absence of clinically approved small-molecule inhibitors. In this study, we explored drug repurposing as a pragmatic approach to address this gap, leveraging FDA-approved drugs to accelerate the identification of potential telomerase inhibitors. Using a structure-based drug discovery framework, we screened the DrugBank database through a previously validated pharmacophore model for the FVYL pocket in the hTERT thumb domain, the established binding site of BIBR1532. This was followed by molecular docking, pharmacokinetic filtering, and molecular dynamics (MD) simulations to evaluate the stability of protein-ligand complexes. Binding free energy calculations (MM-PBSA and MM-GBSA) were employed for cross-validation, identifying five promising candidates. Experimental validation using the Telomerase Repeat Amplification Protocol (TRAP) assay confirmed the inhibitory potential of Raltitrexed, showing significant inhibition with IC
Tạo bộ sưu tập với mã QR

THƯ VIỆN - TRƯỜNG ĐẠI HỌC CÔNG NGHỆ TP.HCM

ĐT: (028) 36225755 | Email: tt.thuvien@hutech.edu.vn

Copyright @2024 THƯ VIỆN HUTECH