An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer

Jina Kim; Hayoung Hwang; Heeseok Yoon; Jae Eon Lee; Ji Min Oh; Hongchan An; Hyun Dong Ji; Seungmi Lee; Eunju Cha; Min Jung Ma; Dong Su Kim; Su Jeong Lee; Tara Man Kadayat; Jaeyoung Song; Sang Woo Lee; Jae Han Jeon; Keun Gyu Park; In Kyu Lee; Yong Hyun Jeon; Jungwook Chin; Sung Jin Cho

doi:10.1016/j.ejmech.2020.112501

An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer

Jina Kim, Hayoung Hwang, Heeseok Yoon, Jae Eon Lee, Ji Min Oh, Hongchan An, Hyun Dong Ji, Seungmi Lee, Eunju Cha, Min Jung Ma, Dong Su Kim, Su Jeong Lee, Tara Man Kadayat, Jaeyoung Song, Sang Woo Lee, Jae Han Jeon, Keun Gyu Park, In Kyu Lee, Yong Hyun Jeon, Jungwook ChinSung Jin Cho

Department of Medicine

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

12 Scopus citations

Abstract

Estrogen-related receptor gamma (ERRγ) is the NR3B subgroup of associated transcription factors. In this report, a new generation of a potent and selective ERRγ inverse agonist (25) with good biocompatibility was proposed. We also explored the potential of the newly developed compound 25 in the PDTC model to expand the original indications from ATC. In addition, an X-ray crystallographic study of the ligand and ERRγ co-complex showed that 25 completely binds to the target protein (PDB 6KNR). Its medicinal chemistry, including a distinctive structural study to in vivo results, denotes that 25 may be directed towards the development of a pivotal treatment for ERRγ-related cancers.

Original language	English
Article number	112501
Journal	European Journal of Medicinal Chemistry
Volume	205
DOIs	https://doi.org/10.1016/j.ejmech.2020.112501
State	Published - 1 Nov 2020

Keywords

ADMET
ATC
ERRγ inverse agonist
NIS
PDTC
X-ray crystallography

UN SDGs

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

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10.1016/j.ejmech.2020.112501

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Kim, J., Hwang, H., Yoon, H., Lee, J. E., Oh, J. M., An, H., Ji, H. D., Lee, S., Cha, E., Ma, M. J., Kim, D. S., Lee, S. J., Kadayat, T. M., Song, J., Lee, S. W., Jeon, J. H., Park, K. G., Lee, I. K., Jeon, Y. H., ... Cho, S. J. (2020). An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer. European Journal of Medicinal Chemistry, 205, Article 112501. https://doi.org/10.1016/j.ejmech.2020.112501

@article{53ea3e83a44a4b2a91195dc93004cfa0,

title = "An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer",

abstract = "Estrogen-related receptor gamma (ERRγ) is the NR3B subgroup of associated transcription factors. In this report, a new generation of a potent and selective ERRγ inverse agonist (25) with good biocompatibility was proposed. We also explored the potential of the newly developed compound 25 in the PDTC model to expand the original indications from ATC. In addition, an X-ray crystallographic study of the ligand and ERRγ co-complex showed that 25 completely binds to the target protein (PDB 6KNR). Its medicinal chemistry, including a distinctive structural study to in vivo results, denotes that 25 may be directed towards the development of a pivotal treatment for ERRγ-related cancers.",

keywords = "ADMET, ATC, ERRγ inverse agonist, NIS, PDTC, X-ray crystallography",

author = "Jina Kim and Hayoung Hwang and Heeseok Yoon and Lee, {Jae Eon} and Oh, {Ji Min} and Hongchan An and Ji, {Hyun Dong} and Seungmi Lee and Eunju Cha and Ma, {Min Jung} and Kim, {Dong Su} and Lee, {Su Jeong} and Kadayat, {Tara Man} and Jaeyoung Song and Lee, {Sang Woo} and Jeon, {Jae Han} and Park, {Keun Gyu} and Lee, {In Kyu} and Jeon, {Yong Hyun} and Jungwook Chin and Cho, {Sung Jin}",

note = "Publisher Copyright: {\textcopyright} 2020 Elsevier Masson SAS",

year = "2020",

month = nov,

day = "1",

doi = "10.1016/j.ejmech.2020.112501",

language = "English",

volume = "205",

journal = "European Journal of Medicinal Chemistry",

issn = "0223-5234",

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

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Kim, J, Hwang, H, Yoon, H, Lee, JE, Oh, JM, An, H, Ji, HD, Lee, S, Cha, E, Ma, MJ, Kim, DS, Lee, SJ, Kadayat, TM, Song, J, Lee, SW, Jeon, JH, Park, KG, Lee, IK, Jeon, YH, Chin, J & Cho, SJ 2020, 'An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer', European Journal of Medicinal Chemistry, vol. 205, 112501. https://doi.org/10.1016/j.ejmech.2020.112501

TY - JOUR

T1 - An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer

AU - Kim, Jina

AU - Hwang, Hayoung

AU - Yoon, Heeseok

AU - Lee, Jae Eon

AU - Oh, Ji Min

AU - An, Hongchan

AU - Ji, Hyun Dong

AU - Lee, Seungmi

AU - Cha, Eunju

AU - Ma, Min Jung

AU - Kim, Dong Su

AU - Lee, Su Jeong

AU - Kadayat, Tara Man

AU - Song, Jaeyoung

AU - Lee, Sang Woo

AU - Jeon, Jae Han

AU - Park, Keun Gyu

AU - Lee, In Kyu

AU - Jeon, Yong Hyun

AU - Chin, Jungwook

AU - Cho, Sung Jin

PY - 2020/11/1

Y1 - 2020/11/1

N2 - Estrogen-related receptor gamma (ERRγ) is the NR3B subgroup of associated transcription factors. In this report, a new generation of a potent and selective ERRγ inverse agonist (25) with good biocompatibility was proposed. We also explored the potential of the newly developed compound 25 in the PDTC model to expand the original indications from ATC. In addition, an X-ray crystallographic study of the ligand and ERRγ co-complex showed that 25 completely binds to the target protein (PDB 6KNR). Its medicinal chemistry, including a distinctive structural study to in vivo results, denotes that 25 may be directed towards the development of a pivotal treatment for ERRγ-related cancers.

AB - Estrogen-related receptor gamma (ERRγ) is the NR3B subgroup of associated transcription factors. In this report, a new generation of a potent and selective ERRγ inverse agonist (25) with good biocompatibility was proposed. We also explored the potential of the newly developed compound 25 in the PDTC model to expand the original indications from ATC. In addition, an X-ray crystallographic study of the ligand and ERRγ co-complex showed that 25 completely binds to the target protein (PDB 6KNR). Its medicinal chemistry, including a distinctive structural study to in vivo results, denotes that 25 may be directed towards the development of a pivotal treatment for ERRγ-related cancers.

KW - ADMET

KW - ATC

KW - ERRγ inverse agonist

KW - NIS

KW - PDTC

KW - X-ray crystallography

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U2 - 10.1016/j.ejmech.2020.112501

DO - 10.1016/j.ejmech.2020.112501

M3 - Article

C2 - 32758860

AN - SCOPUS:85088866426

SN - 0223-5234

VL - 205

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

M1 - 112501

ER -

An orally available inverse agonist of estrogen-related receptor gamma showed expanded efficacy for the radioiodine therapy of poorly differentiated thyroid cancer

Abstract

Keywords

UN SDGs

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