{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["31(12)"],"submitter":["Kong X"],"pubmed_abstract":["As a key regulator for hormone activity, human aldo-keto reductase family 1 member C3 (AKR1C3) plays crucial roles in the occurrence of various hormone-dependent or independent malignancies. It is a promising target for treating castration-resistant prostate cancer (CRPC). However, the development of AKR1C3 specific inhibitors remains challenging due to the high sequence similarity to its isoform AKR1C2. Here, we performed a combined in silico study to illuminate the inhibitory preference of 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids for AKR1C3 over AKR1C2, of which compound 38 can achieve up to 5000-fold anti-AKR1C3 selectivity. Our umbrella sampling (US) simulations together with end-point binding free energy calculation MM/GBSA uncover that the high inhibition selectivity "],"journal":["Protein science : a publication of the Protein Society"],"pagination":["e4499"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC9679971"],"repository":["biostudies-literature"],"pubmed_title":["Computational modeling studies reveal the origin of the binding preference of 3-(3,4-di hydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids for AKR1C3 over its isoforms."],"pmcid":["PMC9679971"],"pubmed_authors":["Li PK","Zhuang T","Li C","Wu S","Xing E","Cheng X","Kong X"],"additional_accession":[]},"is_claimable":false,"name":"Computational modeling studies reveal the origin of the binding preference of 3-(3,4-di hydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids for AKR1C3 over its isoforms.","description":"As a key regulator for hormone activity, human aldo-keto reductase family 1 member C3 (AKR1C3) plays crucial roles in the occurrence of various hormone-dependent or independent malignancies. It is a promising target for treating castration-resistant prostate cancer (CRPC). However, the development of AKR1C3 specific inhibitors remains challenging due to the high sequence similarity to its isoform AKR1C2. Here, we performed a combined in silico study to illuminate the inhibitory preference of 3-(3,4-dihydroisoquinolin-2(1H)-ylsulfonyl)benzoic acids for AKR1C3 over AKR1C2, of which compound 38 can achieve up to 5000-fold anti-AKR1C3 selectivity. Our umbrella sampling (US) simulations together with end-point binding free energy calculation MM/GBSA uncover that the high inhibition selectivity ","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022 Dec","modification":"2026-05-27T18:51:20.634Z","creation":"2025-04-06T14:09:21.488Z"},"accession":"S-EPMC9679971","cross_references":{"pubmed":["36335585"],"doi":["10.1002/pro.4499"]}}