Discovery, design and synthesis of Y-shaped peroxisome proliferator- activated receptor δ agonists as potent anti-obesity agents in vivo

Jungyeob Ham; Hoosang Hwang; Euno Kim; Jeong Ah Kim; Sung Jin Cho; Jaeyoung Ko; Woojin Lee; Jaehwan Lee; Harish Holla; Joydeep Banerjee; Seokho Kim; Inho Yang; Hyun Joo Lee; Kyoungjin Shin; Hyukjae Choi; Sang Jip Nam; Jungae Tak; Dongyup Hahn; Taekyung Oh; Dong Hwan Won; Tae Gu Lee; Jihye Choi; Mi Sun Park; Chaok Seok; Jungwook Chin; Heonjoong Kang

doi:10.1016/j.ejmech.2012.03.055

Discovery, design and synthesis of Y-shaped peroxisome proliferator- activated receptor δ agonists as potent anti-obesity agents in vivo

Jungyeob Ham
, Hoosang Hwang
, Euno Kim
, Jeong Ah Kim
, Sung Jin Cho
, Jaeyoung Ko
, Woojin Lee
, Jaehwan Lee
, Harish Holla
, Joydeep Banerjee
, Seokho Kim
, Inho Yang
, Hyun Joo Lee
, Kyoungjin Shin
, Hyukjae Choi
, Sang Jip Nam
, Jungae Tak
, Dongyup Hahn
, Taekyung Oh
, Dong Hwan Won

Tae Gu Lee, Jihye Choi, Mi Sun Park, Chaok Seok, Jungwook Chin, Heonjoong Kang

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

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 EC₅₀ values between 1 and 523 nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPARδ agonists with 10⁴-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.

Original language	English
Pages (from-to)	190-202
Number of pages	13
Journal	European Journal of Medicinal Chemistry
Volume	53
DOIs	https://doi.org/10.1016/j.ejmech.2012.03.055
State	Published - Jul 2012
Externally published	Yes

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

Anti-obesity
GW501516
Marine natural products
Nuclear receptors
PPARδ

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10.1016/j.ejmech.2012.03.055

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Ham, J., Hwang, H., Kim, E., Kim, J. A., Cho, S. J., Ko, J., Lee, W., Lee, J., Holla, H., Banerjee, J., Kim, S., Yang, I., Lee, H. J., Shin, K., Choi, H., Nam, S. J., Tak, J., Hahn, D., Oh, T., ... Kang, H. (2012). Discovery, design and synthesis of Y-shaped peroxisome proliferator- activated receptor δ agonists as potent anti-obesity agents in vivo. European Journal of Medicinal Chemistry, 53, 190-202. https://doi.org/10.1016/j.ejmech.2012.03.055

@article{d03162d3a7db4acca99c5b3acb936ced,

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 EC50 values between 1 and 523 nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPARδ agonists with 104-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.",

keywords = "Anti-obesity, GW501516, Marine natural products, Nuclear receptors, PPARδ",

author = "Jungyeob Ham and Hoosang Hwang and Euno Kim and Kim, \{Jeong Ah\} and Cho, \{Sung Jin\} and Jaeyoung Ko and Woojin Lee and Jaehwan Lee and Harish Holla and Joydeep Banerjee and Seokho Kim and Inho Yang and Lee, \{Hyun Joo\} and Kyoungjin Shin and Hyukjae Choi and Nam, \{Sang Jip\} and Jungae Tak and Dongyup Hahn and Taekyung Oh and Won, \{Dong Hwan\} and Lee, \{Tae Gu\} and Jihye Choi and Park, \{Mi Sun\} and Chaok Seok and Jungwook Chin and Heonjoong Kang",

year = "2012",

month = jul,

doi = "10.1016/j.ejmech.2012.03.055",

language = "English",

volume = "53",

pages = "190--202",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

publisher = "Elsevier Masson s.r.l.",

}

Ham, J, Hwang, H, Kim, E, Kim, JA, Cho, SJ, Ko, J, Lee, W, Lee, J, Holla, H, Banerjee, J, Kim, S, Yang, I, Lee, HJ, Shin, K, Choi, H, Nam, SJ, Tak, J, Hahn, D, Oh, T, Won, DH, Lee, TG, Choi, J, Park, MS, Seok, C, Chin, J & Kang, H 2012, 'Discovery, design and synthesis of Y-shaped peroxisome proliferator- activated receptor δ agonists as potent anti-obesity agents in vivo', European Journal of Medicinal Chemistry, vol. 53, pp. 190-202. https://doi.org/10.1016/j.ejmech.2012.03.055

TY - JOUR

T1 - Discovery, design and synthesis of Y-shaped peroxisome proliferator- activated receptor δ agonists as potent anti-obesity agents in vivo

AU - Ham, Jungyeob

AU - Hwang, Hoosang

AU - Kim, Euno

AU - Kim, Jeong Ah

AU - Cho, Sung Jin

AU - Ko, Jaeyoung

AU - Lee, Woojin

AU - Lee, Jaehwan

AU - Holla, Harish

AU - Banerjee, Joydeep

AU - Kim, Seokho

AU - Yang, Inho

AU - Lee, Hyun Joo

AU - Shin, Kyoungjin

AU - Choi, Hyukjae

AU - Nam, Sang Jip

AU - Tak, Jungae

AU - Hahn, Dongyup

AU - Oh, Taekyung

AU - Won, Dong Hwan

AU - Lee, Tae Gu

AU - Choi, Jihye

AU - Park, Mi Sun

AU - Seok, Chaok

AU - Chin, Jungwook

AU - Kang, Heonjoong

PY - 2012/7

Y1 - 2012/7

N2 - We have discovered and demonstrated the in vitro and in vivo PPARδ-selective activity of novel Y-shaped agonists. These compounds activated hPPARδ with EC50 values between 1 and 523 nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPARδ agonists with 104-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.

AB - We have discovered and demonstrated the in vitro and in vivo PPARδ-selective activity of novel Y-shaped agonists. These compounds activated hPPARδ with EC50 values between 1 and 523 nM. Surprisingly, compounds 10a, 11d, 11e and 11f were the most potent and most selective hPPARδ agonists with 104-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.

KW - Anti-obesity

KW - GW501516

KW - Marine natural products

KW - Nuclear receptors

KW - PPARδ

UR - https://www.scopus.com/pages/publications/84861584756

U2 - 10.1016/j.ejmech.2012.03.055

DO - 10.1016/j.ejmech.2012.03.055

M3 - Article

C2 - 22534184

AN - SCOPUS:84861584756

SN - 0223-5234

VL - 53

SP - 190

EP - 202

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

ER -

Discovery, design and synthesis of Y-shaped peroxisome proliferator- activated receptor δ agonists as potent anti-obesity agents in vivo

Abstract

UN SDGs

Keywords

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