Predicting Off Target Hits in Drug Discovery
Screening Mutiple Binding Sites for Drug Sunitinib

Sunitinib is a drug approved by the FDA on January 26, 2006, which is for the treatment of renal cell carcinoma (RCC) and imatinib-resistant gastrointestinal stromal tumor (GIST)
Sunitinib has multi-targeted receptors, (RTK, KIT and PDGFR inhibitors etc.)
Sunitinib with KIT protein receptor has 3D structure in PDB (3G0E)
The images of molecule, protein and binding site are displayed below.

 

Sunitinib binding site in 3G0E can be described by PFSC below
The binding pocket is described by three fragments

 

With Probe Binding Site for Drug Discovery (PBSDD) technology, starting from Sunitinib binding site, the PF-PDB database was screened.  About 85,000 protein structures were screened to find out the similar binding site as Sunitinib. >
All results were ranked according the similarity score of PFSA-S and physiochemical property.  
Only structures on top of 85,000 protein structures were selected as higher similarity, which predicted potential binding sites for Sunitinib. Part results are shown below.

 

 

 

amples of the fingerprints of binding sites

 

Samples of alignments for structures with higher similarity score

 

From 200 structures with higher similarity score among 85,000 protein database (0.21%), hit targets were summed as below chart.
Top of chart shows the protein receptors which are detected by bio-assays. It is important that PBSDD result also hit most of these targets.
Bottom of chart is new target which predicted by PBSDD technology here.