title: A novel 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives and pharmacophore model as Wnt2/β-catenin pathway inhibitors in non-small-cell lung cancer cell lines.
abstract: We developed Wnt/β-catenin inhibitors by identifying 13 number of 3-arylethynyl-substituted pyrido[2,3,-b]pyrazine derivatives that were able to inhibit the Wnt/β-catenin signal pathway and cancer cell proliferation. In the optimization process, a series of 2,3,6-trisubstituted pyrido[2,3,-b]pyrazine core skeletons showed were shown to higher activity than 2,3,6-trisubstituted quinoxaline's and thus hold promise for use as potential small-molecule inhibitors of the Wnt/β-catenin signal pathway in non-small-cell lung cancer cell (NSCLC) lines. And we have studied the pharmacophore mapping for compound 954, which presented the highest activity with a fit value of 2.81. The pharmacophore mapping for the compounds including 954, pyrido[2,3,-b]pyrazine core had hydrogen-bond acceptor site and hydrophobic center roles.
authors.affiliation: Center for Innovative Drug Library Research, Dongguk University, Pil-dong 3-ga, Jung-gu, Seoul 100-715, Republic of Korea. ydgong@dongguk.edu
authors.forename: Young-Dae
authors.initials: YD
authors.lastname: Gong
authors.forename: Mi-Sook
authors.initials: MS
authors.lastname: Dong
authors.forename: Sang-Bum
authors.initials: SB
authors.lastname: Lee
authors.forename: Nayeon
authors.initials: N
authors.lastname: Kim
authors.forename: Mi-Seon
authors.initials: MS
authors.lastname: Bae
authors.forename: Nam-Sook
authors.initials: NS
authors.lastname: Kang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D008958:Models, Molecular; D015394:Molecular Structure; D011719:Pyrazines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051176:beta Catenin / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011719:Pyrazines; D011725:Pyridines; D051153:Wnt Proteins; D051176:beta Catenin