dbtop: Topomer similarity searching of conventional structure databases

Cramer, Richard D.; Jilek, Robert J.; Andrews, Katherine M.

doi:10.1016/s1093-3263(01)00146-2

Cited by 51 publications

(51 citation statements)

References 12 publications

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“…Datasets were also clustered using 2D fingerprints and tanimoto similarity. Nisius and Goller (2009) used the Tripos Topomer Search technology (Cramer et al, 2002) to design a modeling approach termed topoHERG. This method screens reference datasets for molecules similar to a query compound and returns pharmacophore and shapebased distances between a query molecule and its neighbors.…”

Section: Prediction Of Human Ether-a-go-go Rrelated Gene Bindingmentioning

confidence: 99%

Computational Methods in Drug Discovery

Sliwoski

Kothiwale

Meiler

et al. 2014

Pharmacological Reviews

1,711

1,101

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Section: Prediction Of Human Ether-a-go-go Rrelated Gene Bindingmentioning

confidence: 99%

Computational Methods in Drug Discovery

Sliwoski

Kothiwale

Meiler

et al. 2014

Pharmacological Reviews

1,711

1,101

View full text Add to dashboard Cite

“…Ligand-based virtual screening for analogs similar to purmorphamine or the previously established osteoinductive substances #3 or #70 from Lee et al [2008] was performed by Biognos AB using the Topomer software (Tripos Inc., St. Louis, Mo., USA) [Cramer et al, 2002;2004]. The template molecules, as well as each molecule in the database, were fragmented and one conformation for each fragment was considered.…”

Section: Purmorphamine Analog Screeningmentioning

confidence: 99%

Virtual Ligand-Based Screening Reveals Purmorphamine Analogs with the Capacity to Induce the Osteogenic Differentiation of Human Mesenchymal Stem Cells

Granéli

Karlsson²,

Lindahl³

et al. 2012

Cells Tissues Organs

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Human mesenchymal stem cells (hMSCs) have extensive proliferative capacity, are able to self-renew and have the potential to differentiate into cells of the connective tissue lineages. These properties make them a putative cell type for tissue engineering applications, as well as a possible in vivo target for the pharmaceutical modulation of the differentiation processes.The aim of this study was to find one or more small-molecule substances that would enhance the osteogenic differentiation of hMSCs in vitro. The strategy used here was ligand-based virtual screening for substances similar to the previously suggested osteoinductive purmorphamine followed by an in vitro screening of the selected analogs in hMSCs isolated from bone marrow. We investigated the osteoinductive capacity of several purmorphamine analogs by determining the protein and gene expression of markers for osteogenic differentiation as well as the extracellular matrix (ECM) mineralization of these cells. Treatment with two candidate substances or purmorphamine resulted in increased levels of alkaline phosphatase (ALP) activity compared to the control. Other purmorphamine analogs demonstrated higher calcium deposition in the ECM after 5 weeks of osteogenic differentiation, compared to both purmorphamine and the control condition. The resulting substances, which had positive effects on the osteogenic differentiation, are promising as possible modes of treatment for bone-related diseases or defects that target and enhance the osteogenic differentiation of MSCs, in vitro or in vivo. Furthermore, the concept of combining the virtual ligand-based screening method with in vitro screening, using human adult stem cells as a possible strategy for drug discovery, is demonstrated.

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“…In Topomers (dbtop) [29,30] from Tripos query and data set, molecules are fragmented across all acyclic bonds, the open valence is capped, and one single 3D conformation of each fragment is generated with the CONCORD program. The fragments are first oriented according to the open valence bond and then the rest is oriented using a rule-based scheme.…”

Section: Methodsmentioning

confidence: 99%