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A Series of Indole-Thiazole Derivatives Act as GPER Agonists and Inhibit Breast Cancer Cell Growth.

ABSTRACT: The G protein-coupled estrogen receptor (GPER, GPR30) represents a promising target for the treatment of estrogen receptor ? and ? negative breast cancers. Previously reported agonists of GPER have shown that activation of GPER inhibits breast cancer cell proliferation. We report herein a new GPER agonist scaffold based upon in silico pharmacophore screening. Three of these compounds were found to increase cAMP at similar levels as the known GPER-selective agonist G-1. Compound 5 was found to be selective for GPER (over estrogen receptor ? and ?) and inhibit breast cancer cell proliferation at levels consistent with G-1. Docking studies go on to suggest that both 5 and G-1 bind within the same binding pocket in GPER and point to possible key residues that are important in GPER activation.

SUBMITTER: O'Dea A

PROVIDER: S-EPMC6142053 | biostudies-literature | 2018 Sep

REPOSITORIES: biostudies-literature

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A Series of Indole-Thiazole Derivatives Act as GPER Agonists and Inhibit Breast Cancer Cell Growth.

O'Dea Austin A Sondergard Chelsea C Sweeney Patrick P Arnatt Christopher Kent CK

ACS medicinal chemistry letters 20180904 9

The G protein-coupled estrogen receptor (GPER, GPR30) represents a promising target for the treatment of estrogen receptor α and β negative breast cancers. Previously reported agonists of GPER have shown that activation of GPER inhibits breast cancer cell proliferation. We report herein a new GPER agonist scaffold based upon in silico pharmacophore screening. Three of these compounds were found to increase cAMP at similar levels as the known GPER-selective agonist G-1. Compound <b>5</b> was foun ...[more]

PMID: 30258538

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