Target putative

Fig. 4.1. Cellular model illustrating cell types in vascular wall involved in vasorelaxation induced by SERMs. Putative targets of SERMs are indicated within cyan tags. SERMs directly affect L-type VDCC, BK fil subunit in smooth muscle cells, and ER in endothelial cells. L-type VDCC L-type voltage-dependent calcium channel BK calcium-activated large conductance K+ channel PKG protein kinase G eNOS endothelial nitric oxide synthase GC soluble guanylate cyclase cGMP cyclic GM P V electrochemical membrane potential ER estrogen receptor. See text for further details...

Scientists carry out searches on databases. Each EST of interest can be compared with sequences in proteins, and the degree of match can be determined. A technique called threading is used. This involves using data on three-dimensional (3D) protein structure, coupled with knowledge of the physicochemical properties of amino acids, to determine if the amino acid sequence is likely to fold in the same way as a sequence for which the structure is known. In this way, more information about the putative target protein can be assessed. 

More recently, in silico target validation has been used. This is similar to the method discussed for ESTs. The DNA sequence of the putative target is compared with those of known liganded receptors. If homologies (similarities) of sequences and structures are determined, they can provide clues to ligands that are likely to interact with the target. 

Having validated the inverse screening approach for fom unrelated ligands, a prospective screening was carried out to identify the putative targets for representative compounds of a scaffold-focused combinatorial library (Fig. 11). 

Nuovo GJ (2010) In situ detection of microR-NAs in parafiin embedded, formalin fixed tissues and the co-localization of their putative targets. Methods 52 307-315... 

A state of consciousness depends on the intact function of the complex neural networks that underlie alertness, learning and memory. General anesthetics appear to interrupt synaptic transmission within these systems. Multiple ion channels and receptors that mediate and modulate synaptic transmission are putative targets for general anesthetics. All general anesthetics are not alike in the way they alter consciousness. For example, ketamine induces a state of... 

Atack, J.R., Broughton, H.B., and Pollack, S.J. (1995) Inositol monophosphatase—a putative target for Li-H in the treatment of bipolar disorder. Trends Neurosci, 18 343-349. 

Drug Putative Target or Mechanism of Action, Comment... 

It is evident that flavonoid ingestion, either through the diet or as pure compounds or active principles in phytomedicines, results in the presence of these biologically active compounds in the gastrointestinal tract during a certain period of time. Thus, this system can be considered as the first putative target of flavonoid effects, especially if we consider the results obtained from the different studies which deal with the bioavailability of flavonoids, (extensively reviewed by Hollman and Katan [25]). 

The phosphate derivatives (301)-(303) of 6-0-(2-hydroxyethyl)cyclohexane-l,2,4,6-tetraol have been synthesized as inositol monophosphatase inhibitors, the putative target for lithium therapy.270 Compounds (303) and (302) are the most potent examples of a primary alkyl phosphate and phosphate monanion inhibitor so far reported. 

J.D., Garcia, G.A., Reuter, K., Klebe, G. From hit to lead de novo design based on virtual screening hits of inhibitors of tRNA-guanine transglycosylase, a putative target of shigellosis therapy. Helv. Chim. Acta 2003, 86, 1435-1452. 

Shirataki H, Kaibuchi K, Sakoda T et al (1993) Rabphilin-3A, a putative target protein for smg p25A/rab3A p25 small GTP-binding protein related to synaptotagmin. Mol Cell Biol 13 2061-8... 

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