The
Kinase Knowledgebase (KKB) is Eidogen-Sertanty's database of kinase structure-activity and chemical synthesis data. The KKB represents the first gene-family
wide implementation of our proprietary web-based technology
for the capture, curation, and display of biological
activity and chemical synthesis data from scientific
literature and patents.
Content & Curation
Currently
the Kinase Knowledgebase Q1 2008 Release includes the following data:
- Journal articles and patents: 4,127
- Number of Biological Activity Data Points: >345,000
- Number of unique kinase molecules with annotated assay data: >118,000
- Number of all unique kinase molecules from patents
and articles (with or without bio-activity data): >463,000
- Number of unique kinase targets with assay data: 309
- Number of annotated assay protocols: 15,365
- Number of annotated chemical reactions: 2,365
For a more comprehensive list of all SAR data points for each target, please contact us.
Computational scientists will find Eidogen-Sertanty's
knowledgebase to be an exceptional source for high
quality training sets to build predictive QSAR models. All
SAR data undergoes rigorous quality control. Every
data point is associated with detailed bio assay protocols
and is classified by:
- Standardized gene name
- Binding mode
- Assay type
- Additional in vitro data, e.g. cellular potency/cell
line
- Efficacy data in appropriate animal models
We select the most relevant data such as in vitro enzyme
activity data - in particular IC50 values - for the
development of QSAR models (ePotency and eSelectivity),
and cell-based activity and toxicity data for the development
of advanced activity models (eADME and eTox).
Our curation process also captures chemical synthesis
steps for those kinase inhibitors with detailed experimental
procedures. Chemistry information is organized by protocols
of generic reaction sequences incorporating synthetically
feasible reagents that are reported in the context
of the claims of a patent. This not only generates
all specific examples from a patent, but also a comprehensive
ensemble of structures - the patent space - that can
possibly be made by the reported synthetic methodology,
and which are potentially relevant within the biological
activity class. Synthetic pathways leading to these
molecules are structurally linked to the biological
information.
Download a white paper describing the Kinase Knowledgebase
content development, target standardization, and classification
process.
Value to Drug Discovery
The knowledgebase is designed to support medicinal
chemists during all project stages of drug
discovery. We work closely with our clients to ensure
that they receive all the relevant information around
their targets and anti-targets.
At the start of a lead discovery project, the Kinase
Knowledgebase provides an overview of published
knowledge and patents around kinase targets of therapeutic
importance, enabling a
detailed understanding of the knowledge space around the target of
interest and the relevant anti-targets.
The presentation of inhibitor structural data makes
it easy to group known inhibitors in scaffold groups
and lay out a project plan around patentable chemotypes.
In the lead discovery and optimization phase of a project,
the knowledgebase helps to prioritize compounds
for synthesis or purchase based on their predicted
properties. Based on the high quality content we have
captured, we have developed nearly 50 kinase-specific eScreen® modules
useful for potency and selectivity prediction, lead
optimization and scaffold jumping.
Applications
- Map out patent landscape around inhibitors for kinase targets of interest.
- Organize known inhibitors into scaffold groups, including detailed synthesis steps.
- Use predicted properties and eScreen® data to prioritize compounds for synthesis or purchase.
- Utilize large quantities of descriptive SAR data to enable scaffold jumping.
Data Access
The Kinase Knowledgebase is designed such that it can
be used by every scientist in the drug discovery team,
even those without special training in the computational
sciences. The KKB can either be accessed online
through the ARK™ platform or purchased for integration
into in-house databases (MDL-ISIS/Host or Daylight-DayCart
Cartridge ready, and SD or TDT ASCII file format).
To find out more about licensing terms and arrange a product demonstration, please contact us at info@eidogen-sertanty.com
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