Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.7.11.26 (GSK)
 6,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Four members of the tandem-pore potassium channel family of Arabidopsis thaliana (TPK1, 2, 3, and 5) reside in the vacuolar membrane, whereas TPK4 is a plasma membrane K(+)-channel. By constructing chimeras between TPK1 and TPK4, we attempted to identify channel domains involved in the trafficking process and found that the TPK1 cytoplasmic C-terminal domain (CT) is critical for the ER- as well as Golgi-sorting steps. Following site-directed mutagenesis, we identified a diacidic motif (DLE) required for ER-export of TPK1. However, this diacidic motif in the C-terminus is not conserved among other members of the TPK family, and TPK3 sorting is independent of its CT. Moreover, the 14-3-3 binding site of TPK1, essential for channel activation, is not involved in channel sorting.
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PMID:Targeting of vacuolar membrane localized members of the TPK channel family. 1982 94

In November 2009, Human Genome Sciences and Glaxo-Smith Kline [HGS (Rockville, Maryland) and GSK, respectively] announced that Belimumab, a neutralizing antibody to the tumour necrosis factor (TNF)-like ligand, B-cell activating factor (BAFF belonging to the TNF family, also named BLyS), met the primary endpoints in two phase III clinical trials in systemic lupus erythematosus (SLE, lupus). In March 2011, Belimumab was approved by the US Federal Drug Agency for treatment of SLE patients; this was followed in May with approval by the European Medicines Agency for use in the European Union. This is an exciting development as it is the first successful late-stage clinical trial in SLE in over 40 years. In the light of this breakthrough, we review the key data and research outcomes and examine how blocking BAFF in patients with SLE significantly improves clinical outcomes.
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PMID:BAFF/BLyS inhibitors: A new prospect for treatment of systemic lupus erythematosus. 2264 24

On 17 May, Human Genome Sciences (HGS) formally rejected a $2.6 billion unsolicited takeover offer by GlaxoSmithKline. The Maryland-based biotech firm had long partnered with the UK drug giant to develop drugs including Benlysta (belimumab), HGS's first drug on the market and the first new medicine approved to fight lupus in 50 years. But, at $13 a share, GSK's bid was deemed "inadequate" by the HGS board. Recent history in the biotech sector shows how high the stakes are in such negotiations. Since last November, six biopharma buyouts have exceeded $1 billion each, with Gilead Sciences' purchase last year of the hepatitis C specialist Pharmasset topping the charts at a whopping $11.2 billion, the highest ever paid for a clinical-stage biotech and an 89% premium to its share price at the time. More recently, in April AstraZeneca paid $1.3 billion for Ardea Biosciences, a company with cancer and gout drugs in the pipeline but nothing on the market.One person watching the upward clime of such deals is biopharma analyst Joseph Schwartz, a managing director at Leerink Swann in Boston. Mark Ratner sought out Schwartz, who was named the top stock picker for pharmaceuticals in the last year's FT/StarMine Analyst Awards, for his views on what's behind the recent buyout spending.
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PMID:Straight talk with...Joseph Schwartz. 2267 87

Cyclosporin A is an immunosuppressant drug that is used not only in solid transplant rejection, but also in moderate and severe forms of psoriasis, pyoderma, lupus or arthritis. Serious side effects of the drug such as skin cancer or gingival hyperplasia probably start with the latent proliferation process. Little is known about the influence of cyclosporin A on molecular signaling in epidermal tissue. Thus, the aim of this study was to estimate the influence of cyclosporin A on the process of proliferation in normal human dermal fibroblasts. Fibroblasts were cultured in a liquid growth medium in standard conditions. Cyclosporin A was added to the culture after the confluence state. Survival and proliferation tests on human dermal fibroblast cells were performed. Total RNA was extracted from fibroblasts, based on which cDNA and cRNA were synthesized. The obtained cRNA was hybridized with the expression microarray HGU-133A_2.0. Statistical analysis of 2734 mRNAs was performed by the use of GeneSpring 13.0 software and only results with p < 0.05 were accepted. Analysis of variance with Tukey post hoc test with Benjamini-Hochberg correction for all three (8, 24, 48 h) culture stages (with and without cyclosporin A) was performed to lower the number of statistically significant results from 679 to 66, and less. Between statistically and biologically significant mRNAs down-regulated were EGRJ, BUBIB, MKI67, CDK1, TTK, E2F8, TPX2, however, the INSIG1, FOSL1, HMOX1 were up-regulated. The experiment data revealed that cyclosporin A up-regulated FOSL1 in the first 24 h, afterwards down-regulating its expression. The HMOX1 gene was up-regulated in the first stage of the experiment (CsA 8 h), however, after the next 16 h of culture time its expression was down-regulated (CsA 24 h), to finally increased in the later time period. The results indicate that cyclosporin A had a significant effect on proliferation in normal human dermal fibroblasts through the changes in the expression of genes related to the cell cycle and transcription regulation process.
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PMID:CYCLOSPORIN A AFFECTS THE PROLIFERATION PROCESS IN NORMAL HUMAN DERMAL FIBROBLASTS. 2700 1