title: Novel indole alpha-methylene-gamma-lactones as potent inhibitors for AKT-mTOR signaling pathway kinases.
abstract: In an effort to generate novel anticancer agents, a series of hybrids of alpha-methylene-gamma-lactones and 2-phenyl indoles has been synthesized and evaluated for inhibition activities on the phosphorylation of AKT, mTOR, p70S6 kinase, and 4E-BP1. The results indicate that substitutes on the gamma-position of lactones have a rather significant influence on inhibition activities.
authors.affiliation: State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Graduate School of the CAS, 555 Zuchongzhi Road, Shanghai 201203, PR China.
authors.forename: Huasheng
authors.initials: H
authors.lastname: Ding
authors.forename: Chao
authors.initials: C
authors.lastname: Zhang
authors.forename: Xihan
authors.initials: X
authors.lastname: Wu
authors.forename: Chunhao
authors.initials: C
authors.lastname: Yang
authors.forename: Xiongwen
authors.initials: X
authors.lastname: Zhang
authors.forename: Jian
authors.initials: J
authors.lastname: Ding
authors.forename: Yuyuan
authors.initials: Y
authors.lastname: Xie
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000494:pharmacology; D002352:Carrier Proteins / Q000187:drug effects / Q000378:metabolism; D018797:Cell Cycle Proteins; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D007783:Lactones / Q000138:chemical synthesis* / Q000494:pharmacology; D010750:Phosphoproteins / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology; D011494:Protein Kinases / Q000187:drug effects* / Q000378:metabolism; D038762:Ribosomal Protein S6 Kinases, 70-kDa / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013329:Structure-Activity Relationship; D058570:TOR Serine-Threonine Kinases
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D002352:Carrier Proteins; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D007211:Indoles; D007783:Lactones; D010750:Phosphoproteins; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases; C546842:MTOR protein, human; D038762:Ribosomal Protein S6 Kinases, 70-kDa; D058570:TOR Serine-Threonine Kinases