Activity receptor profiling

Molecular structure has been shown to influence absorption. By examining the structural characteristics of drugs that were in use, certain common characteristics of well-absorbed molecules were identified, commonly referred to as the rule of five. Some investigators have used this as a basis for characterizing the drug-likeness of a lead chemical. Other factors also come into play including receptor activity, metabolism profile and for CNS-active compounds, an ability to cross the blood-brain barrier. 

The metabolism of heroin is of interest in connection with its pharmacological activities. Earlier opiate -receptor binding studies led to the belief that heroin is a prodrug acting through its metabolites 6-acetylmorphine and morphine [95]. However, heroin is now known to activate (5-receptors, whereas morphine activates -receptor and 6-acetylmorphine acts at both receptor types [96]. Thus, the pharmacodynamic profile of heroin results from both direct and metabolite-mediated effects. 

Macrophage presence and reactivity in tissue sites are elicited though different combinations of effector molecules (e.g., cytokines, chemokines) acting on specific receptors thus, the expression and presence of given membrane receptors on macrophage cell surfaces correlate to specific (acquired) functions and activation profiles.18 Furthermore, macrophage maturity and/or differentiation state is/are often characterized based on the presence or absence of specific surface receptors (e.g., F4/80 +, Mac-1 + Figure 2.1).61 Receptor profiles vary between cells of different maturity, primary and secondary derivation, and between cell lines.62... 

Ploug M, Rahbek-Nielsen H, Nielsen PF, Roepstorff P, Dano K. Glycosylation profile of a recombinant urokinase-type plasminogen activator receptor expressed in Chinese hamster ovary cells. J Biol Chem 1998 273(22) 13933-13943. 

A compromise between large unbiased and small focused libraries has become popular, especially for pharmaceutical applications. These biased-targeted libraries are not inspired by a precise structural information, but rather by general information regarding similar classes of targets (e.g., kinases or 7-transmembrane receptors) or by the desired activity-unrelated profile that a drug must possess (e.g., the molecular weight, the partition coefficient, the water solubihty, and other physicochemical properties). Their main properties are fisted in Fig. 5.6. 

Di Martino, M.T., Arbitrio, M., Guzzi, P.H., Leone, E., Baudi, F., Piro, E., Prantera, T., Cucinotto, L, Calimeri, T., Rossi, M., Veltri, P., Cannataro, M., et at (2011). A peroxisome proliferator-activated receptor gamma (PPARG) polymorphism is associated with zoledronic acid-related osteonecrosis of the j aw in multiple myeloma patients analysis by DMET microarray profiling. Br J Haematol 154 529-533. 

Perhaps the environmental chemical most studied with regard to effects on the immune system has been 2,3,7,8-tetrachlorodibenzo-p-dioxin, which is also known as TCDD or dioxin . While it appears that dioxin may affect multiple cell types, it is apparent that the B cell is an especially sensitive target. The mechanism of action for the immunotoxic effects of dioxin remains poorly understood. It is well established that many of the actions of dioxin, including inhibition of the primary antibody response, are mediated by a specific cytosolic receptor, termed the aryl hydrocarbon receptor (AhR). AhR exhibits a profile of activity similar to steroid receptors in that the ligand-activated receptor undergoes a nuclear... 

Di Martino MT, Arbitrio M, Guzzi PH et al (2011) A peroxisome proliferator-activated receptor gamma (PPARG) polymorphism is associated with zoledronic acid-related osteonecrosis of the jaw in multiple myeloma patients analysis by DMET microarray profiling. Br J Haematol 154 529-533... 

A peroxisome proliferator-activated receptor a/y dual agonist with a unique in vitro profile and potent glucose and lipid effects in rodent models of type 2 diabetes and dyslipidemia. Molecular Endocrinology, 19, 1593-1605. 

Trentin L, Miorin M, Facco M, et al. (2007) Multiple myeloma plasma cells show different chemokine receptor profiles at sites of disease activity. Br J Haematol 138 594-602... 

Multiple myeloma plasma cells show different chemokine receptor profiles at sites of disease activity. Br J Haematol 138 594. 

Chu, R., Lim, H., Brumfield, L., Liu, H., Herring, C., Ulintz, P., Reddy, J. K., and Davison, M. (2004) Protein profiling of mouse livers with peroxisome proliferator-activated receptor alpha activation. Mol Cell Biol 24, 6288-97. 

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