title: 2-(2-Methylfuran-3-carboxamido)-3-phenylpropanoic acid, a potential CYP26A1 inhibitor to enhance all-trans retinoic acid-induced leukemia cell differentiation based on virtual screening and biological evaluation.
abstract: To develop new CYP26A1 inhibitors, a three-cycle virtual screening was carried out based on the constructed homology model of human CYP26A1 using Dock, Fred, Gold and AutoDock. Twenty-two compounds exhibited high scores and reasonable binding modes in molecular docking were purchased from Specs Company. Eighteen compounds were tested their abilities to enhance ATRA-induced differentiation in human acute promyelocytic leukemia NB4 cells. Eight of them enhanced the ability of ATRA to induce differentiation at concentrations of 0.5 and 1 μM. Among these compounds, 2-(2-methylfuran-3-carboxamido)-3-phenylpropanoic acid (S8) is of most effective in blocking ATRA breaking down in NB4 cells based on the LC-MS/MS assay.
authors.affiliation: Key Laboratory of Structure-Based Drugs Design & Discovery of Ministry of Education, School of Pharmaceutical Engineering, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, PR China.
authors.forename: Fengrong
authors.initials: F
authors.lastname: Li
authors.forename: Dongmei
authors.initials: D
authors.lastname: Zhao
authors.forename: Jinhong
authors.initials: J
authors.lastname: Ren
authors.forename: Feiyue
authors.initials: F
authors.lastname: Hao
authors.forename: Guyue
authors.initials: G
authors.lastname: Liu
authors.forename: Shengfei
authors.initials: S
authors.lastname: Jin
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Jing
authors.forename: Maosheng
authors.initials: M
authors.lastname: Cheng
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000737:chemistry; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D062105:Molecular Docking Simulation; D010649:Phenylalanine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D000072516:Retinoic Acid 4-Hydroxylase; D014212:Tretinoin / Q000494:pharmacology*
chemical_list: C584670:2-(2-methylfuran-3-carboxamido)-3-phenylpropanoic acid; D000970:Antineoplastic Agents; D065607:Cytochrome P-450 Enzyme Inhibitors; D004791:Enzyme Inhibitors; D010649:Phenylalanine; D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D000072516:Retinoic Acid 4-Hydroxylase