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Life Chemicals offers four kinds of targeted libraries in accordance with expected biological activity of compounds: General Targeted Libraries, Sharp-Focused Libraries, CUTE Targeted Libraries and Murcko Algorithm Targeted Libraries.
General Targeted Libraries are meant to be the broad pre-selection of compounds with certain biological activity from our main data base. The have been made using receptor based or ligand based approach.
General Targeted Libraries composed by ligand based approach include:
- Ion Channel Targeted Library (60 000 compounds): 2D Fingerprint similarity search.
- GPCR Targeted Library (34 000 compounds): 2D Fingerprint similarity search and Pharmacophore approach.
- Nuclear Receptor Targeted Library (40 000 compounds, 16 receptors): 2D Fingerpint similarity search
- Protease Targeted Libraries (3 000 compounds): Trypsin-like serine proteases, matrix metalloproteases, carboxypeptidases. Composed by functional groups filtering.
- Anticancer Targeted Library (23 000 compounds, 2D Fingerpint similarity search)
- Adenosine receptor agonist/antagonist focused compound libraries (1 300 compounds): analysis of structure-activity relationships (SAR)
The following General Targeted Libraries have been created using the receptor based approach:
- Kinase Targeted Library (CDK2, GSK3, PKB, SRC (2 structures), EGFR): docking and subsequent pharmacophore filtering (32 000 compounds).
- Nuclear Receptor Targeted Library (Thyroid Hormone Receptor, Human Glucocorticoid (2 forms), Retinoic Acid Receptor): docking and filtering by 4 pharmacophore models.
CUTE Targeted Libraries
CUTE Targeted Libraries is a brand new product created in co-operation with Chemotargets, Barcelona-based (Catalonia, Spain) in silico pharmacology company. These libraries are based on an innovative concept derived from SHED molecular descriptors.based on an innovative concept derived from SHED molecular descriptors. You can download a pdf file with some information about them here.
Murcko Algorithm Targeted Libraries
Life Chemicals offers a set of targeted libraries specifically designed and synthesized to target both the aminergic GPCR receptors and the peptidergic GPCR receptors. The compounds have been designed by applying the Murcko fragmentation algorithm on a large set of known GPCR-ligands. The libraries will be made available on a non-exclusive basis. Follow-up synthesis of hits can be performed at reduced cost as the chemistry around the presented scaffolds has been evaluated at Life Chemicals. So we don’t only offer the libraries, but also the follow up in the hit-to-lead finding process as well as lead optimization.
Sharp-Focused Libraries - Joint Project Life Chemicals Inc. with Otava:
The receptor-based target-focused libraries are generated on the basis of computational estimation of compound interaction with 1 certain target of protein family (Sharp focusing). The core of these libraries design is flexible docking. After the docking, "rescoring" algorithm is applied.
The "rescoring" procedure includes correction of final summation of interaction energies (score) according to structural features of each ligand. At the final stage we scan each docking complex for H-bond(s) formed between ligand and critical (key) aminoacid residue(s) of the protein active site.
Detailed analysis of each protein-ligand complex obtained with docking allows design of unique focused libraries. The first seven sharp-focused libraries have been completed:
- Human Fibroblast Growth Factor Receptor 1 Tyrosine Kinase (FGFR1K) focused library (1 622 compounds).
- 3-Phosphoinositide-dependent kinase-1 (PDK-1) focused library (1 704 compounds).
- cAMP dependent protein kinase (PKA ) focused library (1 673 compounds)
- Phosphatidylinositol 3-kinase (PI3K) focused library (2 049 compounds)
- Human Janus kinase 2 (JAK 2) focused library (2 109 compounds)
- Aurora B Kinase receptor-based focused library (2 144 compounds)
- Vascular endothelial growth factor receptor (VEGFR) kinase focused library (2 341 compounds)
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