New paper on steroid-regulated gene expression

Recent paper in Molecular Endocrinology 7:1194-206. doi: 10.1210/me.2014-1069:

Research Resource: Modulators of glucocorticoid receptor activity identified by a new high-throughput screening assay

John A. Blackford, Jr., Kyle R. Brimacombe, Edward J. Dougherty , Madhumita Pradhan, Min Shen, Zhuyin Li, Douglas S. Auld, Carson C. Chow, Christopher P. Austin, and S. Stoney Simons, Jr.

Abstract: Glucocorticoid steroids affect almost every tissue-type and thus are widely used to treat a variety of human pathologies. However, the severity of numerous side-effects limits the frequency and duration of glucocorticoid treatments. Of the numerous approaches to control off-target responses to glucocorticoids, small molecules and pharmaceuticals offer several advantages. Here we describe a new, extended high throughput screen in intact cells to identify small molecule modulators of dexamethasone-induced glucocorticoid receptor (GR) transcriptional activity. The novelty of this assay is that it monitors changes in both GR maximal activity (Amax) and EC50, or the position of the dexamethasone dose-response curve. Upon screening 1280 chemicals, ten with the greatest change in the absolute value of Amax or EC50 were selected for further examination. Qualitatively identical behaviors for 60 –90% of the chemicals were observed in a completely different system, suggesting that other systems will be similarly affected by these chemicals. Additional analysis of the ten chemicals in a recently described competition assay determined their kinetically-defined mechanism and site of action. Some chemicals had similar mechanisms of action despite divergent effects on the level of GR-induced product. These combined assays offer a straightforward method of identifying numerous new pharmaceuticals that can alter GR transactivation in ways that could be clinically useful.

Advertisements

2 thoughts on “New paper on steroid-regulated gene expression

  1. as a very serious researcher (i only publish in gigascience, use plink, or use my blogs http://www.santafe.edu or http://www.arxiv.org or its inverse, ww.vixra.org ocassionally look at http://philsci-pitt.edu or fom-list) i heard about half of science friday today, with sean carrol (cal tech), michua kaku (superstrings—–goes back to Nambu),and seth lyod (mit—my niece is dealing with the snow up there and even classes) . ‘the topic was ‘should these scientific ideas be retired’ (amazon book)–by john brockman—‘this idea must die’. peace out—this is just a joke comment.

    Like

  2. ps. its actully http:/philsci-archive.pitt.edu (i disagree with many of he papers on that site—i did take a class in ‘philosophy of space and time’—read stuff by grunbaum, reichenbach, etc even dingle). on npr they said both space and time were outdated ideas. ’emergent spacetime’ is the new jingle.

    Like

Leave a Reply

Fill in your details below or click an icon to log in:

WordPress.com Logo

You are commenting using your WordPress.com account. Log Out / Change )

Twitter picture

You are commenting using your Twitter account. Log Out / Change )

Facebook photo

You are commenting using your Facebook account. Log Out / Change )

Google+ photo

You are commenting using your Google+ account. Log Out / Change )

Connecting to %s