2-Methoxyestradiol and its derivatives inhibit store-operated Ca2+ entry in T cells: identification of a new and potent inhibitor
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2-Methoxyestradiol and its derivatives inhibit store-operated Ca2+ entry in T cells: identification of a new and potent inhibitor. / Löhndorf, Anke; Hosang, Leon; Dohle, Wolfgang; Odoardi, Francesca; Waschkowski, Sissy-Alina; Rosche, Anette; Bauche, Andreas; Winzer, Riekje; Tolosa, Eva; Windhorst, Sabine; Marry, Stephen; Flügel, Alexander; Potter, Barry V L; Diercks, Björn-Philipp; Guse, Andreas H.
In: BBA-MOL CELL RES, Vol. 1868, No. 6, 05.2021, p. 118988.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - 2-Methoxyestradiol and its derivatives inhibit store-operated Ca2+ entry in T cells: identification of a new and potent inhibitor
AU - Löhndorf, Anke
AU - Hosang, Leon
AU - Dohle, Wolfgang
AU - Odoardi, Francesca
AU - Waschkowski, Sissy-Alina
AU - Rosche, Anette
AU - Bauche, Andreas
AU - Winzer, Riekje
AU - Tolosa, Eva
AU - Windhorst, Sabine
AU - Marry, Stephen
AU - Flügel, Alexander
AU - Potter, Barry V L
AU - Diercks, Björn-Philipp
AU - Guse, Andreas H
N1 - Copyright © 2021. Published by Elsevier B.V.
PY - 2021/5
Y1 - 2021/5
N2 - T cell activation starts with formation of second messengers that release Ca2+ from the endoplasmic reticulum (ER) and thereby activate store-operated Ca2+ entry (SOCE), one of the essential signals for T cell activation. Recently, the steroidal 2-methoxyestradiol was shown to inhibit nuclear translocation of the nuclear factor of activated T cells (NFAT). We therefore investigated 2-methoxyestradiol for inhibition of Ca2+ entry in T cells, screened a library of 2-methoxyestradiol analogues, and characterized the derivative 2-Ethyl-3-sulfamoyloxy-17β-cyanomethylestra-1,3,5(10)-triene (STX564) as a novel, potent and specific SOCE inhibitor. STX564 inhibits Ca2+ entry via SOCE without affecting other ion channels and pumps involved in Ca2+ signaling in T cells. Downstream effects such as cytokine expression and cell proliferation were also inhibited by both 2-methoxyestradiol and STX564, which has potential as a new chemical biology tool.
AB - T cell activation starts with formation of second messengers that release Ca2+ from the endoplasmic reticulum (ER) and thereby activate store-operated Ca2+ entry (SOCE), one of the essential signals for T cell activation. Recently, the steroidal 2-methoxyestradiol was shown to inhibit nuclear translocation of the nuclear factor of activated T cells (NFAT). We therefore investigated 2-methoxyestradiol for inhibition of Ca2+ entry in T cells, screened a library of 2-methoxyestradiol analogues, and characterized the derivative 2-Ethyl-3-sulfamoyloxy-17β-cyanomethylestra-1,3,5(10)-triene (STX564) as a novel, potent and specific SOCE inhibitor. STX564 inhibits Ca2+ entry via SOCE without affecting other ion channels and pumps involved in Ca2+ signaling in T cells. Downstream effects such as cytokine expression and cell proliferation were also inhibited by both 2-methoxyestradiol and STX564, which has potential as a new chemical biology tool.
U2 - 10.1016/j.bbamcr.2021.118988
DO - 10.1016/j.bbamcr.2021.118988
M3 - SCORING: Journal article
C2 - 33581218
VL - 1868
SP - 118988
JO - BBA-MOL CELL RES
JF - BBA-MOL CELL RES
SN - 0167-4889
IS - 6
ER -