8-alkylthio-6-thio-substituted theophylline analogues as selective noncompetitive progesterone receptor antagonists.
8-alkylthio-6-thio-substituted theophylline analogues as selective noncompetitive progesterone receptor antagonists.
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DOI：
10.1016/j.steroids.2012.02.003
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发表时间：
2012-05
期刊：
影响因子：
2.7
通讯作者：
Shapiro DJ
中科院分区：
文献类型：
--
作者：
Aninye IO;Berg KC;Mollo AR;Nordeen SK;Wilson EM;Shapiro DJ
The progesterone receptor (PR) plays a key role in reproduction and is important in cancers of the reproductive tract. Current PR antagonists usually compete for progestin binding in the PR ligand-binding pocket and often exhibit cross-binding with other members of the steroid receptor family. Using stably transfected cells expressing reporter genes, a set of ~150 theophylline analogues were screened for their ability to inhibit progesterone, estrogen, glucocorticoid and androgen signaling. The structure-activity studies presented here identify branched 8-alkylthio-6-thio-substitutions of theophylline as selective PR inhibitors. 6-thio-8-(2-ethylbutyl)thiotheophylline (51), the most extensively studied derivative, does not act by competing with progestins for binding in the ligand-binding pocket of PR. It demonstrated the ability to inhibit the mouse mammary tumor virus (MMTV)-luciferase reporter and endogenous PR-regulated alkaline phosphatase activity in T47D breast cancer cells. Compound 51 is the lead member of a novel class of PR inhibitors that act outside the PR ligand-binding pocket, thus serving as a novel probe to investigate PR action and a lead for further development.
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DOI：
10.1006/bbrc.1993.1525
发表时间：
1993-05-14
影响因子：
3.1
作者：
DILORENZO, D;GIANNI, M;GARATTINI, E
通讯作者：
GARATTINI, E
影响因子：
4.1
作者：
FERNLEY, HN;WALKER, PG
通讯作者：
WALKER, PG
影响因子：
6.1
作者：
SHI, YE;LIU, YLE;DICKSON, RB
通讯作者：
DICKSON, RB
影响因子：
4.8
作者：
Kretzer, Nicole M.;Cherian, Milu T.;Shapiro, David J.
通讯作者：
Shapiro, David J.
影响因子：
2.9
作者：
KATZENELLENBOGEN, JA;JOHNSON, HJ;MYERS, HN
通讯作者：
MYERS, HN