title: Discovery, design and synthesis of Y-shaped peroxisome proliferator-activated receptor δ agonists as potent anti-obesity agents in vivo.
abstract: We have discovered and demonstrated the in vitro and in vivo PPARδ-selective activity of novel Y-shaped agonists. These compounds activated hPPARδ with EC(50) values between 1 and 523 nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPARδ agonists with 10(4)-fold selectivity over the other two subtypes, namely, hPPARα and hPPARγ. The PPARδ ligands 10a, 11e and 11f showed good bioavailability and in vivo efficacy.
authors.affiliation: Center for Marine Natural Products and Drug Discovery, School of Earth and Environmental Sciences, Seoul National University, NS-80, Seoul 151-747, Republic of Korea.
authors.forename: Jungyeob
authors.initials: J
authors.lastname: Ham
authors.forename: Hoosang
authors.initials: H
authors.lastname: Hwang
authors.forename: Euno
authors.initials: E
authors.lastname: Kim
authors.forename: Jeong-Ah
authors.initials: JA
authors.lastname: Kim
authors.forename: Sung Jin
authors.initials: SJ
authors.lastname: Cho
authors.forename: Jaeyoung
authors.initials: J
authors.lastname: Ko
authors.forename: Woojin
authors.initials: W
authors.lastname: Lee
authors.forename: Jaehwan
authors.initials: J
authors.lastname: Lee
authors.forename: Harish
authors.initials: H
authors.lastname: Holla
authors.forename: Joydeep
authors.initials: J
authors.lastname: Banerjee
authors.forename: Seokho
authors.initials: S
authors.lastname: Kim
authors.forename: Inho
authors.initials: I
authors.lastname: Yang
authors.forename: Hyun Joo
authors.initials: HJ
authors.lastname: Lee
authors.forename: Kyoungjin
authors.initials: K
authors.lastname: Shin
authors.forename: Hyukjae
authors.initials: H
authors.lastname: Choi
authors.forename: Sang-Jip
authors.initials: SJ
authors.lastname: Nam
authors.forename: Jungae
authors.initials: J
authors.lastname: Tak
authors.forename: Dongyup
authors.initials: D
authors.lastname: Hahn
authors.forename: Taekyung
authors.initials: T
authors.lastname: Oh
authors.forename: Dong Hwan
authors.initials: DH
authors.lastname: Won
authors.forename: Tae Gu
authors.initials: TG
authors.lastname: Lee
authors.forename: Jihye
authors.initials: J
authors.lastname: Choi
authors.forename: Mi Sun
authors.initials: MS
authors.lastname: Park
authors.forename: Chaok
authors.initials: C
authors.lastname: Seok
authors.forename: Jungwook
authors.initials: J
authors.lastname: Chin
authors.forename: Heonjoong
authors.initials: H
authors.lastname: Kang
mesh_terms: D000818:Animals; D019440:Anti-Obesity Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D060326:Chemistry Techniques, Synthetic; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D006801:Humans; D051379:Mice; D008958:Models, Molecular; D009765:Obesity / Q000188:drug therapy / Q000209:etiology; D047494:PPAR delta / Q000819:agonists* / Q000737:chemistry; D011487:Protein Conformation
chemical_list: D019440:Anti-Obesity Agents; D047494:PPAR delta