Lead discovery partnership with a European, inter-governmental research organization by cost- and resource-efficient screening and identification of a specific kinase inhibitor within three months.
Many protein kinases are validated intervention points for contemporary drug discovery approaches; however active site similarities often lead to a lack of selectivity and thus, unwanted side effects in the clinic. Our client identified a specific kinase receptor that would provide the desired selectivity, and was looking for a cost- and resource-efficient way to expand their chemical structural variety through natural products. Discovering selective inhibitors as potential drug candidates was envisioned.
Bicoll provided 1,000 Profiles™ from its proprietary small molecule natural product library BILOBAC N to the clientís screening program, which resulted in 18 hit clusters showing specific kinase activity. Because of the high hit rate of 1.8%, the client elected to focus on 4 hit clusters for isolation and structure elucidation.
Within three months and a second round of screening, Bicoll identified and structurally elucidated two pure compounds with interesting structural motifs for the clientís further development programs. Subsequent investigation of Bicollís pure natural compound database, using the newly found structural motifs, led to the testing of additional compounds.
The search for novel ligands binding to a well-characterized class of orphan nuclear receptors that are relevant targets for diseases with an inflammatory component is the goal of an international lead discovery cooperation, which consists of a listed European biopharmaceutical company, European academic institutes, and Bicoll.
The international cooperation is financially co-supported through the European Union for its uniqueness and lowering risks.
The biopharmaceutical company has identified a specific nuclear receptor as a relevant target in inflammatory processes. As this nuclear receptor is lacking identified natural or synthetic ligands, the main challenge was to deorphanize the receptor by screening a very high number of compounds with the most broad structure diversity.
Bicoll was approached for a joint research project based on the screening of its highly diversified library of plant metabolites BILOBAC N.
With the delivery of an extensive number of selected Profiles™ from its fractionated natural product compound database BILOBAC N, the project was able to identify several novel compounds. Bicoll's unique Profiles™ technology has demonstrated its ability to be successfully integrated into screening systems for modern drug discovery. The program is currently in progress and first active compounds as ligands could be delivered.