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- W2022707619 endingPage "226" @default.
- W2022707619 startingPage "199" @default.
- W2022707619 abstract "Cyclic AMP (cAMP) and cyclic GMP (cGMP) are key second messengers involved in a multitude of cellular events. From the wealth of synthetic analogs of cAMP and cGMP, only a few have been explored with regard to their therapeutic potential. Some of the first-generation cyclic nucleotide analogs were promising enough to be tested as drugs, for instance N(6),O(2)'-dibutyryl-cAMP and 8-chloro-cAMP (currently in clinical Phase II trials as an anticancer agent). Moreover, 8-bromo and dibutyryl analogs of cAMP and cGMP have become standard tools for investigations of biochemical and physiological signal transduction pathways. The discovery of the Rp-diastereomers of adenosine 3',5'-cyclic monophosphorothioate and guanosine 3',5'-cyclic monophosphorothioate as competitive inhibitors of cAMP- and cGMP-dependent protein kinases, as well as subsequent development of related analogs, has proven very useful for studying the molecular basis of signal transduction. These analogs exhibit a higher membrane permeability, increased resistance against degradation, and improved target specificity. Furthermore, better understanding of signaling pathways and ligand/protein interactions has led to new therapeutic strategies. For instance, Rp-8-bromo-adenosine 3',5'-cyclic monophosphorothioate is employed against diseases of the immune system. This review will focus mainly on recent developments in cyclic nucleotide-related biochemical and pharmacological research, but also highlights some historical findings in the field." @default.
- W2022707619 created "2016-06-24" @default.
- W2022707619 creator A5003663371 @default.
- W2022707619 creator A5004638394 @default.
- W2022707619 creator A5024835945 @default.
- W2022707619 creator A5049654018 @default.
- W2022707619 date "2000-08-01" @default.
- W2022707619 modified "2023-10-05" @default.
- W2022707619 title "Cyclic nucleotide analogs as biochemical tools and prospective drugs" @default.
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