Ullah, Shafi; Khan, Shafi Ullah; Khan, Abbas; Junaid, Muhammad; Rafiq, Humaira; Htar, Thet Thet; Zhao, Yaxue; Shah, Syed Adnan Ali; Wadood, Abdul published the artcile< Prospect of Anterior Gradient 2 homodimer inhibition via repurposing FDA-approved drugs using structure-based virtual screening>, Related Products of 6054-98-4, the main research area is anterior Gradient homodimer inhibition FDA approved drug structure screening; AGR2 homodimer; Cancer; Dimer inhibitor; Drug repositioning; Virtual screening.
Anterior Gradient 2 (AGR2) has recently been reported as a tumor biomarker in various cancers, i.e., breast, prostate and lung cancer. Predominantly, AGR2 exists as a homodimer via a dimerization domain (E60-K64); after it is self-dimerized, it helps FGF2 and VEGF to homo-dimerize and promotes the angiogenesis and the invasion of vascular endothelial cells and fibroblasts. Up till now, no small mol. has been discovered to inhibit the AGR2-AGR2 homodimer. Therefore, the present study was performed to prepare a validated 3D structure of AGR2 by homol. modeling and discover a small mol. by screening the FDA-approved drugs library on AGR2 homodimer as a target protein. Thirteen different homol. models of AGR2 were generated based on different templates which were narrowed down to 5 quality models sorted by their overall Z-scores. The top homol. model based on PDB ID = 3PH9 was selected having the best Z-score and was further assessed by Verify-3D, ERRAT and RAMPAGE anal. Structure-based virtual screening narrowed down the large library of FDA-approved drugs to ten potential AGR2-AGR2 homodimer inhibitors having FRED score lower than – 7.8 kcal/mol in which the top 5 drugs’ binding stability was counter-validated by mol. dynamic simulation. To sum up, the present study prepared a validated 3D structure of AGR2 and, for the first time reported the discovery of 5 FDA-approved drugs to inhibit AGR2-AGR2 homodimer by using structure-based virtual screening. Moreover, the binding of the top 5 hits with AGR2 was also validated by mol. dynamic simulation. A validated 3D structure of Anterior Gradient 2 (AGR2) was prepared by homol. modeling, which was used in virtual screening of FDA-approved drugs library for the discovery of prospective inhibitors of AGR2-AGR2 homodimer.
Molecular Diversity published new progress about Anterior gradient protein 2 Role: BSU (Biological Study, Unclassified), BIOL (Biological Study). 6054-98-4 belongs to class alcohols-buliding-blocks, and the molecular formula is C14H8N2Na2O6, Related Products of 6054-98-4.
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Alcohols – Chemistry LibreTexts