Current section of case studies provides examples of some projects of successful R&D projects (like, kinase inhibitor, orphan nuclear receptors and lead optimization) done by Bicoll.

Case study 1

Background: Lead discovery partnership with a European, inter-governmental research organization. Three months to identify specific kinase inhibitor, based on cost- and resource-efficient screening.

Results: 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. Moreover, the client was looking for a cost- and resource-efficient way to expand its chemical structural variety through natural products. Vision was to discover selective inhibitors as potential drug candidates.

Bicoll provided 1,000 Bicoll Plant Profiles™ from its proprietary small molecule natural product library BILOBAC N™ to client’s screening program. The result was: 18 hit clusters showing specific kinase activity. Because of the high hit rate of 1.8%, the client selected to focus on 4 hit clusters for isolation and structure elucidation.Case study 1 - kinase inhibitors

Within three months and a second round of screening, Bicoll identified and structurally elucidated two pure compounds. They had interesting structural motifs for further development programs. Subsequent investigation of Bicoll’s pure natural compound database, using the newly found structural motifs, led to the testing of additional compounds.

Case study 2

Background: An international lead discovery cooperation consisted of a listed European biopharmaceutical company, European academic institutes and Bicoll. The goal was to search for novel ligands binding to a well-characterized class of orphan nuclear receptors that are relevant targets for diseases with an inflammatory component. European Union financially co-supported mentioned above international cooperation for its uniqueness and lowering risks.

Case study 2 - orphan nuclear receptorsResults: The biopharmaceutical company identified a specific nuclear receptor as a relevant target in inflammatory processes. Due to the fact, that this nuclear receptor is lacking identified natural or synthetic ligands, the main challenge was to de-orphanize the receptor by screening a very high number of compounds with the most broad structure diversity.

Therefore, Bicoll was approached for a joint research project based on the screening of its highly diversified library of plant metabolites BILOBAC N™. As a result, with the delivery of an extensive number of selected Plant Profiles™ the project identified several novel compounds. They rooted from fractionated natural product compound database BILOBAC N™. Bicoll’s unique Plant Profiles™ technology has demonstrated its ability to be successfully integrated into screening systems for modern drug discovery. The program is currently in progress. Above all, active compounds as ligands were delivered.

Case study 3

Background: A biotech company in North America needs a target-focused molecular library for lead optimization.

Result: Case study 3 - lead optimization, FTE services Request was to build-up a target-focused synthetic library within tight timelines, inclusive the follow up compounds for the subsequent biological tests up to 100 g scale. Bicoll has planned the project hand-in-hand with US-partner Ricerca Biosciences. Furthermore, the client chose to start with 2 FTE’s at Bicoll’s Shanghai site and eventually upgraded to 10 FTE’s. In addition, together with the client and our partner Ricerca, Bicoll has set-up an efficient project management through its headquarters in Europe. Moreover, it included synthetic strategies as well as management of workflow, communication and reporting between the US, Europe and China. Due to this strategical geographical position, Munich headquarters guarantee to the client a convenient overlap in working hours for teleconferences, weekly written reports, meeting requirements for patent filing and essential IP protection. Shanghai MedChem team ensures high quality, synthetic strategic support and the achievement of the desired timelines with its manpower.