cgp-74588 and Parkinson-Disease

cgp-74588 has been researched along with Parkinson-Disease* in 1 studies

Other Studies

1 other study(ies) available for cgp-74588 and Parkinson-Disease

Article	Year
Discovery of LRRK2 inhibitors using sequential in silico joint pharmacophore space (JPS) and ensemble docking. Bioorganic & medicinal chemistry letters, 2015, Jul-01, Volume: 25, Issue:13 Joint pharmacophore space (JPS), ensemble docking and sequential JPS-ensemble docking were used to select three panels of compounds (10 per panel) for evaluation as LRRK2 inhibitors. These computational methods identified four LRRK2 inhibitors with IC50 values <12μM. The sequential JPS-ensemble docking predicted the majority of active hits. One of the inhibitors (Z-8205) identified using this method was also found to inhibit the G2019S mutant of LRRK2 25-fold better than wild-type enzyme. This bias for the G2019S mutant is proposed to arise from an interaction with S2019 in this form of the enzyme. In addition, Z-8205 was found to only inhibit one other kinase when profiled against a panel of 97 kinases at 10μM. Topics: Amino Acid Substitution; Binding Sites; Computer Simulation; Drug Discovery; High-Throughput Screening Assays; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Models, Molecular; Mutant Proteins; Parkinson Disease; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Structural Homology, Protein; Structure-Activity Relationship	2015

Article

Year

Discovery of LRRK2 inhibitors using sequential in silico joint pharmacophore space (JPS) and ensemble docking.

Bioorganic & medicinal chemistry letters, 2015, Jul-01, Volume: 25, Issue:13

Joint pharmacophore space (JPS), ensemble docking and sequential JPS-ensemble docking were used to select three panels of compounds (10 per panel) for evaluation as LRRK2 inhibitors. These computational methods identified four LRRK2 inhibitors with IC50 values <12μM. The sequential JPS-ensemble docking predicted the majority of active hits. One of the inhibitors (Z-8205) identified using this method was also found to inhibit the G2019S mutant of LRRK2 25-fold better than wild-type enzyme. This bias for the G2019S mutant is proposed to arise from an interaction with S2019 in this form of the enzyme. In addition, Z-8205 was found to only inhibit one other kinase when profiled against a panel of 97 kinases at 10μM.

Topics: Amino Acid Substitution; Binding Sites; Computer Simulation; Drug Discovery; High-Throughput Screening Assays; Humans; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2; Models, Molecular; Mutant Proteins; Parkinson Disease; Protein Kinase Inhibitors; Protein Serine-Threonine Kinases; Structural Homology, Protein; Structure-Activity Relationship

2015