Receptor-based drug discovery

The new paradigm for orphan receptor-based drug discovery is shown diagrammatically (Fig. 5). A first step toward ligand identification for a given orphan... 

Central tendency, 226-227 Chemical genomics, 178 Chemical tools, in target-based drug discovery, 178-179 Chemokine C receptor type 1, 133 Chemokine receptors, 6, 44, 53, 129, 132, 177... 

Tang Herbal, 147 Target-based drug discovery biological targets, 180-184 chemical end point in, 180 chemical tools, 178-179 definition of, 5 description of, 175-177 linear approach, 176 orphan receptors, 180 preclinical process in, 176-177 random variation in gene expression, 178... 

Manas ES, Mewshaw RE, Harris HA, Malamas MS. Isoform specificity The design of estrogen receptor-b selective compounds. In Chapter 8 Editor, Hubbard, RE. London Structure-based drug discovery an overview. RSC Publishing. 2006 219-56. 

This raises the key test of target validation. Does a compound that has the appropriate potency, selectivity, and ADME properties, that is active in "predictive" animal models, and is free of other systems toxicology work in the targeted human disease state This is the ultimate test of a target-based drug discovery program. With the considerable compound attrition rates in moving from animals to diseased humans, this has not proven to be a predictable transition. A case in point is that of the NKl receptor activated by the peptide, substance P. 

Multicomponent reactions in alkaloid-based drug discovery 12KGS38. Neoclerodanes as atypical opioid receptor ligands 13JMC3435. 

Kubinyi H1998. Structure-based Design of Enzyme Inhibitors and Receptor Ligands. Current Opinion i. Drug Discovery and Development 1 5-15. 

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