title: Therapeutic and pharmacokinetic characterizations of an anti-amyloidogenic bis-styrylbenzene derivative for Alzheimer's disease treatment.
abstract: Alzheimer's disease drug discovery regarding exploration into the molecules and processes has focused on the intrinsic causes of the brain disorder correlated with the accumulation of amyloid-β. An anti-amyloidogenic bis-styrylbenzene derivative, KMS80013, showed excellent oral bioavailability (F=46.2%), facilitated brain penetration (26%, iv) in mouse and target specific in vivo efficacy in acute AD mouse model attenuating the cognitive deficiency in Y-maze test. Acute toxicity (LD50 >2000 mg/kg) and hERG channel inhibition (14% at 10 μM) results indicated safety of KMS80013.
authors.affiliation: Center for Neuro-Medicine, Brain Science Institute, Korea Institute of Science and Technology, Hwarangno 14-gil 5, Seongbuk-gu, Seoul 136-791, Republic of Korea.
authors.forename: Seong Rim
authors.initials: SR
authors.lastname: Byeon
authors.forename: Hyunjin Vincent
authors.initials: HV
authors.lastname: Kim
authors.forename: Mijin
authors.initials: M
authors.lastname: Jeon
authors.forename: Young Gil
authors.initials: YG
authors.lastname: Ahn
authors.forename: Maeng Sup
authors.initials: MS
authors.lastname: Kim
authors.forename: Jae Yang
authors.initials: JY
authors.lastname: Kong
authors.forename: Hye Yun
authors.initials: HY
authors.lastname: Kim
authors.forename: Young Soo
authors.initials: YS
authors.lastname: Kim
authors.forename: Dong Jin
authors.initials: DJ
authors.lastname: Kim
mesh_terms: D000284:Administration, Oral; D000544:Alzheimer Disease / Q000188:drug therapy; D000814:Aniline Compounds / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D000818:Animals; D001555:Benzene Derivatives / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use; D001921:Brain / Q000378:metabolism; D004195:Disease Models, Animal; D051638:Ether-A-Go-Go Potassium Channels / Q000037:antagonists & inhibitors / Q000378:metabolism; D006207:Half-Life; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D013267:Stilbenes / Q000737:chemistry* / Q000493:pharmacokinetics / Q000627:therapeutic use
chemical_list: D000814:Aniline Compounds; D001555:Benzene Derivatives; D051638:Ether-A-Go-Go Potassium Channels; C584757:KMS80013; D013267:Stilbenes