title: Discovery, Optimization, and Biological Evaluation of Sulfonamidoacetamides as an Inducer of Axon Regeneration.
abstract: Axon regeneration after injury in the central nervous system is hampered in part because if an age-dependent decline in the intrinsic axon growth potential, and one of the strategies to stimulate axon growth in injured neurons involves pharmacological manipulation of implicated signaling pathways. Here we report phenotypic cell-based screen of chemical libraries and structure-activity-guided optimization that resulted in the identification of compound 7p which promotes neurite outgrowth of cultured primary neurons derived from the hippocampus, cerebral cortex, and retina. In an animal model of optic nerve injury, compound 7p was shown to induce growth of GAP-43 positive axons, indicating that the in vitro neurite outgrowth activity of compound 7p translates into stimulation of axon regeneration in vivo. Further optimization of compound 7p and elucidation of the mechanisms by which it elicits axon regeneration in vivo will provide a rational basis for future efforts to enhance treatment strategies.
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion , 147 Gwanggyo-ro, Suwon, Korea 16229.
authors.forename: Jin-Mo
authors.initials: JM
authors.lastname: Ku
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion , 147 Gwanggyo-ro, Suwon, Korea 16229.
authors.forename: Kyuhee
authors.initials: K
authors.lastname: Park
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion , 147 Gwanggyo-ro, Suwon, Korea 16229.
authors.forename: Jung Hun
authors.initials: JH
authors.lastname: Lee
authors.forename: Kyong Jin
authors.initials: KJ
authors.lastname: Cho
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion , 147 Gwanggyo-ro, Suwon, Korea 16229.
authors.forename: Yeon-Ju
authors.initials: YJ
authors.lastname: Nam
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion , 147 Gwanggyo-ro, Suwon, Korea 16229.
authors.forename: Dae-Youn
authors.initials: DY
authors.lastname: Jeong
authors.forename: Yu-Han
authors.initials: YH
authors.lastname: Kim
authors.affiliation: Department of Applied Chemistry, Ajou University , 206 Worldcup-ro, Suwon, Korea 16499.
authors.forename: SoonJung
authors.initials: S
authors.lastname: Kwon
authors.affiliation: Department of Applied Chemistry, Ajou University , 206 Worldcup-ro, Suwon, Korea 16499.
authors.forename: Ju-Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion , 147 Gwanggyo-ro, Suwon, Korea 16229.
authors.forename: Jungeun
authors.initials: J
authors.lastname: Yang
authors.affiliation: Department of Pharmacy, Hanyang University , 55 Hanyangdaehak-ro, Ansan, Korea 15588.
authors.forename: Tae-Gyu
authors.initials: TG
authors.lastname: Nam
authors.affiliation: Department of Applied Chemistry, Ajou University , 206 Worldcup-ro, Suwon, Korea 16499.
authors.forename: Sung-Hwa
authors.initials: SH
authors.lastname: Yoon
authors.forename: Sangmee
authors.initials: S
authors.lastname: Ahn
authors.affiliation: Bio-Center, Gyeonggi Institute of Science and Technology Promotion , 147 Gwanggyo-ro, Suwon, Korea 16229.
authors.forename: Yongmun
authors.initials: Y
authors.lastname: Choi
mesh_terms: D000081:Acetamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D001369:Axons / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D055808:Drug Discovery; D051379:Mice; D015394:Molecular Structure; D009416:Nerve Regeneration / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*
chemical_list: C000619428:2-(N-(2-methoxyphenyl)-4-methylphenylsulfonamido)-N-(4-methoxypyridin-3-yl)acetamide; D000081:Acetamides; D013449:Sulfonamides