title: Macrocyclic compounds as anti-cancer agents: design and synthesis of multi-acting inhibitors against HDAC, FLT3 and JAK2.
abstract: A novel series of macrocyclic compounds were designed and synthesized as multi-target inhibitors targeting HDAC, FLT3 and JAK2. Some of these compounds exhibited potent HDAC inhibition as well as FLT3 and JAK2 inhibition under both cell-free and cellular conditions. In vitro antiproliferative assay indicated that these compounds were interestingly more cytotoxic to MV4-11 cells bearing FLT3-ITD mutation and HEL cells bearing JAK2(V617F) mutation.
authors: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors: Cheng-Qing
authors: CQ
authors: Ning
authors: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors: Cheng
authors: C
authors: Lu
authors: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors: Liang
authors: L
authors: Hu
authors: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors: Yan-Jing
authors: YJ
authors: Bi
authors: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors: Lei
authors: L
authors: Yao
authors: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors: Yu-Jun
authors: YJ
authors: He
authors: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
authors: Li-Fei
authors: LF
authors: Liu
authors: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China; Drug Discovery Department, Hisun Group, Taizhou 317700, China.
authors: Xiao-Yu
authors: XY
authors: Liu
authors: School of Pharmaceutical Sciences, Central South University, Changsha 410013, China. Electronic address: niefang_yu@126.com.
authors: Nie-Fang
authors: NF
authors: Yu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006367:HeLa Cells; D056572:Histone Deacetylase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006655:Histone Deacetylases / Q000737:chemistry*; D006801:Humans; D053614:Janus Kinase 2 / Q000037:antagonists & inhibitors*; D047028:Macrocyclic Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D015398:Signal Transduction; D051941:fms-Like Tyrosine Kinase 3 / Q000037:antagonists & inhibitors*
chemical_list: D000970:Antineoplastic Agents; D056572:Histone Deacetylase Inhibitors; D047028:Macrocyclic Compounds; D047428:Protein Kinase Inhibitors; C497970:FLT3 protein, human; D051941:fms-Like Tyrosine Kinase 3; C507924:JAK2 protein, human; D053614:Janus Kinase 2; D006655:Histone Deacetylases
keywords: FLT3; Histone deacetylase; JAK2; Macrocyclic; Multi-target inhibitor