Viswanath, Ambily Nath Indu Lim, Ji Woong Seo, Seon Hee Lee, Jae Yeol Lim, Sang Min Pae, Ae Nim 2024-01-19T22:04:20Z 2024-01-19T22:04:20Z 2021-09-03 2018-08 1747-0277 https://pubs.kist.re.kr/handle/201004/121121 Overexpression GRP78 in a variety of cancers such as glioblastoma, leukemia, lung, prostate, breast, gastric, and colon makes it a prime target for anticancer drug development. Present study reports GRP78-based design of novel anticancer agents using in-silico methods. As a first step toward the work, the interactions between GRP78 and 15 known ligands were modeled by docking simulation. The docked complex, GRP78-13, superior to other compounds with respect to its experimental activity and energy descriptors, was deduced into a structure-based pharmacophore. This hypothesis was applied as a screening filter to Asinex and Chemdiv databases. Finally, 23 hits were tested in vitro. Among these, VH1019 and VH1011 induced a concentration-dependent strong broad antiproliferative effect in glioma (U87-MG), breast cancer (MCF-7), and prostate cancer (DU-145) cell lines as compared to non-tumorigenic control, neonatal foreskin fibroblast (HFF-1). These compounds showed preferential growth inhibition of cancer cells over normal cells. The acetohydrazide derivative VH1019 was identified as a potential new chemotype for GRP78 inhibitors with an IC50 of 12.7 mu M in MCF-7. English WILEY UNFOLDED PROTEIN RESPONSE GLUCOSE-REGULATED PROTEIN-78 STRESS CHAPERONE GRP78/BIP PROSTATE-CANCER CLINICAL-SIGNIFICANCE CARCINOMA-CELLS TERMINAL DOMAIN ACTIVATION EXPRESSION APOPTOSIS GRP78-targeted in-silico virtual screening of novel anticancer agents Article 10.1111/cbdd.13322 1 CHEMICAL BIOLOGY & DRUG DESIGN, v.92, no.2, pp.1555 - 1566 CHEMICAL BIOLOGY & DRUG DESIGN 92 2 1555 1566 scie scopus 000439752200017 2-s2.0-85047783792 Biochemistry & Molecular Biology Chemistry, Medicinal Biochemistry & Molecular Biology Pharmacology & Pharmacy Article UNFOLDED PROTEIN RESPONSE GLUCOSE-REGULATED PROTEIN-78 STRESS CHAPERONE GRP78/BIP PROSTATE-CANCER CLINICAL-SIGNIFICANCE CARCINOMA-CELLS TERMINAL DOMAIN ACTIVATION EXPRESSION APOPTOSIS anticancer agents antiproliferation GRP7S in-silico design structure -based pharmacophore virtual screening