PubMed Health⌕ Search
Home/Archive/PubMed

PubMed · 2818685

Panel discussion. II: Objectives of basic research and predictive value preclinical testing.

F Hoffmeister·G Assmann·G V Born·F R Bühler·W F Caspary·R J Feldmann·W Siegenthaler
View original source ↗Export metadata ↓

Abstract

The source did not provide an abstract. Follow the original record for more information.

Explore related subjects

Drug Evaluation, PreclinicalDrug TherapyPharmacologyPredictive Value of TestsResearchJournal Article

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

F Hoffmeister, G Assmann, G V Born, F R Bühler, W F Caspary, R J Feldmann, W Siegenthaler. 1989. Panel discussion. II: Objectives of basic research and predictive value preclinical testing.. https://pubmed.ncbi.nlm.nih.gov/2818685/

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

PubMed2006

Synthesis and biological activity of PTEN-resistant analogues of phosphatidylinositol 3,4,5-trisphosphate.

The activation of phosphatidylinositol 3-kinase (PI 3-K) and subsequent production of PtdIns(3,4,5)P3 launches a signal transduction cascade that impinges on a plethora of downstream effects on cell physiology. Control of PI 3-K and PtdIns(3,4,5)P3 levels is an important therapeutic target in treatments for allergy, inflammation, cardiovascular, and malignant human diseases. We designed metabolically stabilized, that is, phosphatase resistant, analogues of PtdIns(3,4,5)P3 as probes for long-lived potential agonists or potential antagonists for cellular events mediated by PtdIns(3,4,5)P3. In particular, two types of analogues were prepared containing phosphomimetics that would be selectively resistant to the lipid 3-phosphatase PTEN. The total asymmetric synthesis of the 3-phosphorothioate-PtdIns(3,4,5)P3 and 3-methylenephosphonate-PtdIns(3,4,5)P3 analogues is described. These two analogues showed differential binding to PtdIns(3,4,5)P3 binding modules, and both were potential long-lived activators that mimicked insulin action in sodium transport in A6 cells.

Drug Evaluation, Preclinical↗
PubMed2006

A microfluidics-based mobility shift assay to discover new tyrosine phosphatase inhibitors.

Protein tyrosine phosphatases (PTPs) play key roles in regulating tyrosine phosphorylation levels in cells. Since the discovery of PTP1B as a major drug target for diabetes and obesity, PTPs have emerged as a new and promising class of signaling targets for drug development in a variety of therapeutic areas. The routine use of generic substrate 6,8-difluoro-4-methylumbelliferyl phosphate (DiFMUP) in our hands led to the discovery of very similar and often not very selective molecules. Therefore, to increase the chances to discover novel chemical scaffolds, a side-by-side comparison between the DiFMUP assay and a chip-based mobility shift assay with a specific phosphopeptide was performed, on 1 PTP, using a focused set of compounds. Assay robustness and sensitivity were comparable for both the DiFMUP and mobility shift assays. The off-chip mobility shift assay required a longer development time because of identification, synthesis, and characterization of a specific peptide, and its cost per point was higher. However, although most potent scaffolds found with the DiFMUP assay were confirmed in the mobility shift format, the off-chip mobility shift assay led to the identification of previously unidentified chemical scaffolds with improved druglike properties.

Drug Evaluation, Preclinical↗