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(2011-12-24) - ISBN-13: 978-613-9-38531-7

78. Yngve U, Soderman P, Svensson M, Rosqvist S, Arvidsson PI. Imidazopyridine-based inhibitors of glycogen synthase kinase 3: synthesis and evaluation of amide isostere replacements of the carboxamide scaffold. 2012;9:2442-52

(2011-12-24) - ISBN-13: 978-613-9-37490-8

(2014-03-04) - ISBN-13: 978-3-8484-4592-9

Humoral immunity. In the humoral arm B-lymphocytes are stimulated following recognition of antigen by cell-surface receptors. Antigen receptors on B-lymphocytes are immunoglobulins (Ig). Mature B cells (plasma cells) start the production of antigen-specific immunoglobulins that act as antibodies in serum or along mucosal surfaces. There are five major classes of immunoglobulins: (1) IgM, pentameric Ig with optimal agglutinating capacity, which is first produced after antigenic stimulation; (2) IgG, the main Ig in circulation, which can pass the placenta; (3) IgA, secretory Ig for the protection of mucosal surfaces; (4) IgE, Ig fixing to mast cells or basophilic granulocytes involved in immediate hypersensitivity reactions and (5) IgD, whose major function is as a receptor on B-lymphocytes.

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91. Bidon-Chanal A, Fuertes A, Alonso D, Perez DI, Martinez A, Luque FJ. . Evidence for a new binding mode to GSK-3: allosteric regulation by the marine compound palinurin. 2013;60:479-89

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(2012-04-05) - ISBN-13: 978-3-8484-9872-7

As of February 1995, there are 403 CYP genes in the database, composed of 59 families and 105 subfamilies. These include eight lower eukaryotic families, 15 plant families, and 19 bacterial families. The 15 human P450 gene families comprise 26 subfamilies, 22 of which have been mapped to chromosomal locations throughout most of the genome. Some sequences are clearly orthologous across many species—for example, only one CYP17 (steroid 17α-hydroxylase) gene has been found in all vertebrates examined to date; other sequences within a subfamily are highly duplicated, making the identification of orthologous pairs impossible (e.g., the CYP2C subfamily). Interestingly, human and yeast share an orthologous gene in the CYP51 family. Numerous comprehensive reviews are available for readers seeking further information on the P450 superfamily (Nelson et al. 1993; Nebert et al. 1991; Nebert and McKinnon 1994; Guengerich 1993; Gonzalez 1992).

Compound 1: [N-(5-Phenyl-[1, 3, 4] oxadiazol-2-yl)-benzamide]

First proposed in 1987 and updated on a biannual basis, the nomenclature system is based on divergent evolution of amino acid sequence comparisons between P450 proteins. The P450 genes are divided into families and subfamilies: enzymes within a family display greater than 40% amino acid similarity, and those within the same subfamily display 55% similarity. P450 genes are named with the root symbol CYP followed by an arabic numeral designating the P450 family, a letter denoting the subfamily, and a further arabic numeral designating the individual gene (Nelson et al. 1993; Nebert et al. 1991). Thus, CYP1A1 represents P450 gene 1 in family 1 and subfamily A.

Selected 1,3,4-Oxadiazole Analogs Acting as GSK-3β Inhibitors

The cytochrome P450 superfamily is one of the most studied drug-metabolizing enzyme superfamilies, having a great deal of individual variability in response to chemicals. Cytochrome P450 is a convenient generic term used to describe a large superfamily of enzymes pivotal in the metabolism of innumerable endogenous and exogenous substrates. The term cytochrome P450 was first coined in 1962 to describe an unknown pigment in cells which, when reduced and bound with carbon monoxide, produced a characteristic absorption peak at 450 nm. Since the early 1980s, cDNA cloning technology has resulted in remarkable insights into the multiplicity of cytochrome P450 enzymes. To date, more than 400 distinct cytochrome P450 genes have been identified in animals, plants, bacteria and yeast. It has been estimated that any one mammalian species, such as humans, may possess 60 or more distinct P450 genes (Nebert and Nelson 1991). The multiplicity of P450 genes has necessitated the development of a standardized nomenclature system (Nebert et al. 1987; Nelson et al. 1993).

Cadmiumcyanid-Hexamethylentetramin-Addukts [Cd(CN)2 � 2/3 C6H12N4]

Consumption of alcohol (ethanol) can influence susceptibility to many toxic chemicals in several ways. It can influence the absorption rate and distribution of certain chemicals in the body—for example, increase the gastrointestinal absorption rate of lead, or decrease the pulmonary absorption rate of mercury vapour by inhibiting oxidation which is necessary for retention of inhaled mercury vapour. Ethanol can also influence susceptibility to various chemicals through short-term changes in tissue pH and increase in the redox potential resulting from ethanol metabolism, as both ethanol oxidizing to acetaldehyde and acetaldehyde oxidizing to acetate produce an equivalent of reduced nicotinamide adenine dinucleotide (NADH) and hydrogen (H+ ). Because the affinity of both essential and toxic metals and metalloids for binding to various compounds and tissues is influenced by pH and changes in the redox potential (Telišman 1995), even a moderate intake of ethanol may result in a series of consequences such as: (1) redistribution of long-term accumulated lead in the human organism in favour of a biologically active lead fraction, (2) replacement of essential zinc by lead in zinc-containing enzyme(s), thus affecting enzyme activity, or influence of mobilized lead on the distribution of other essential metals and metalloids in the organism such as calcium, iron, copper and selenium, (3) increased urinary excretion of zinc and so on. The effect of possible aforementioned events can be augmented due to the fact that alcoholic beverages can contain an appreciable amount of lead from vessels or processing (Prpic-Majic et al. 1984; Telišman et al. 1984; 1993).