Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030567 (Parkinson's disease)
 63,064 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recent genome-wide high-throughput (HTS) analyses of protein-protein interactions (PPIs) provide molecular-based information to uncover functions of cells and tissues, such as those of the mammalian brain. However, the HTS PPI data contain much false-negatives and false-positives, which should be primarily addressed in experiments. Integrating PPI data sets with other genome-wide data, such as expression profiles and phenotype data sets, provides novel biological insights. Such integration analysis is valuable for addressing the complexity of the mammalian brain. Discovery of novel interactions followed by a detailed analysis is a successful approach to uncover the function of proteins. For example, extensive PPI screens for parkin, a hereditary Parkinson's disease gene, elucidated the function of parkin as an E3 ubiquitin ligase, with localization and activity regulated by contact with its interaction partners, uncovering at least a part of the molecular pathogenesis of Parkinson's disease.
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PMID:Protein-protein interactions in the mammalian brain. 1684 May 13

Herein we describe the discovery of a series of novel adenosine A(2A) receptor antagonists. A successful hit-to-lead optimization of an HTS hit led to replacement of a metabolically labile ester moiety with a heteroaromatic group. A compound from the series, (cyclopropanecarboxylic acid [5-(5-methyl-[1,2,4]oxadiazol-3-yl)-4-phenyl-thiazol-2-yl]-amide, compound 13), was shown to be effective in reversing haloperidol-induced hypolocomotion, a model of motor dysfunction in Parkinson's Disease.
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PMID:Hit-to-lead optimization of a series of carboxamides of ethyl 2-amino-4-phenylthiazole-5-carboxylates as novel adenosine A2A receptor antagonists. 2065 2

Here we describe the identification, structure-activity relationship and the initial pharmacological characterization of AFQ056/mavoglurant, a structurally novel, non-competitive mGlu5 receptor antagonist. AFQ056/mavoglurant was identified by chemical derivatization of a lead compound discovered in a HTS campaign. In vitro, AFQ056/mavoglurant had an IC50 of 30 nM in a functional assay with human mGluR5 and was selective over the other mGluR subtypes, iGluRs and a panel of 238 CNS relevant receptors, transporter or enzymes. In vivo, AFQ056/mavoglurant showed an improved pharmacokinetic profile in rat and efficacy in the stress-induced hyperthermia test in mice as compared to the prototypic mGluR5 antagonist MPEP. The efficacy of AFQ056/mavoglurant in humans has been assessed in L-dopa induced dyskinesia in Parkinson's disease and Fragile X syndrome in proof of principle clinical studies.
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PMID:AFQ056/mavoglurant, a novel clinically effective mGluR5 antagonist: identification, SAR and pharmacological characterization. 2531 99