What question did this study set out to answer?

To discover novel small-molecule antagonist chemotypes targeting melanin-concentrating hormone receptor 1 (MCH-R1) in the absence of an experimentally determined atomic structure.

January 17, 2008Journal of Medicinal ChemistryOpen Access

Discovery of Novel Chemotypes to a G-Protein-Coupled Receptor through Ligand-Steered Homology Modeling and Structure-Based Virtual Screening

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Authors

CCClaudio N. CavasottoConsejo Nacional de Investigaciones Científicas y Técnicas AOAndrew OrryMolsoft (United States)NMNicholas MurgoloMerck & Co., Inc., Rahway, NJ, USA (United States)

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Implication

Computational screening study reveals novel MCH-R1 antagonist chemotypes using ligand-steered modeling, indicating a tenfold improvement over random screening.

Key Points

To discover novel small-molecule antagonist chemotypes targeting melanin-concentrating hormone receptor 1 (MCH-R1) in the absence of an experimentally determined atomic structure.
Built a ligand-steered homology model of MCH-R1 utilizing information from known ligands to optimize the receptor binding site.
Conducted docking-based virtual screening and evaluated top-scoring compounds experimentally via an MCH-R1 competitive binding assay.
Identified six novel chemotypes that act as low-micromolar affinity antagonists against MCH-R1.
Achieved greater than a 10-fold increase in hit success rate compared with standard random high-throughput screening.

Cite This Study

Cavasotto et al. (2008) studied this question.

synapsesocial.com/papers/6a15b84f5347fbb173a02fe6 https://doi.org/10.1021/jm070759m

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Implication

Computational screening study reveals novel MCH-R1 antagonist chemotypes using ligand-steered modeling, indicating a tenfold improvement over random screening.

Discovery of Novel Chemotypes to a G-Protein-Coupled Receptor through Ligand-Steered Homology Modeling and Structure-Based Virtual Screening

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Implication

Key Points

Cite This Study

Discovery of Novel Chemotypes to a G-Protein-Coupled Receptor through Ligand-Steered Homology Modeling and Structure-Based Virtual Screening

Discussion

Member takes

Implication

Key Points

Cite This Study

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