canSAR: update to the cancer translational research and drug discovery knowledgebase

Abstract

canSAR (http://cansar.icr.ac.uk) is a public, freely available, integrative translational research and drug discovery knowlegebase. canSAR informs researchers to help solve key bottlenecks in cancer translation and drug discovery. It integrates genomic, protein, pharmacological, drug and chemical data with structural biology, protein networks and unique, comprehensive and orthogonal 'druggability' assessments. canSAR is widely used internationally by academia and industry. Here we describe major enhancements to canSAR including new and expanded data. We also describe the first components of canSARblack-an advanced, responsive, multi-device compatible redesign of canSAR with a question-led interface.

Figure 1.

canSAR_black target synopsis showing the navigation wheel and druggability assessment. (A) Target synopsis. Left hand panel displays the icons representing key information on the target as well as a summary description of it. The icons are ticked green and coloured if the target meets certain criteria. For example, if the target is a drug target; if it has a structurally ligandable cavity; if it has bioactive compounds etc. Hover-over of the icons provides the user with the information on each. The right-hand panel provides the new navigation wheel. The user can navigate to key sections of information by clicking on the appropriate sector in the wheel. Here the ligandability information is summarised. First, displaying drugs that are approved or under investigation as well as links to chemical probes; second, summarizing the structurally characterised domains of the protein with a histogram showing the number of available structures for that domain; and whether they contain ligandable cavities; third, the bottom layer provides the chemistry-based assessment and network-based target likeness as a ‘meter’ showing how high the score is for the particular target. (B) Users can navigate into more detailed information about the chains and domains and navigate through all individual structures. (C) Detailed view of individual structures and cavities. Users can explore each of the key properties of these cavities and compare them to known drug target cavities such as kinases and BCL2. (D) Ligandable cavities at protein interfaces can be examined in the same way. All images and raw data are downloadable.

Figure 2.

canSAR_black target synopsis showing the cancer association summary. (A) word-map showing the association of each broad cancer type with the target. The size of the name corresponds to the association score of the target with this cancer. (B) Where drug information is available, drug approval and clinical trial information are listed. (C) Gene expression data and cell-line dependency are among the detailed information provided to help the user examine the evidence of disease association. (D) Gene expression changes of AURKA with progression of clinical stage in adrenal carcinoma.