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BioAscent Collaborates To Identify Potential Cancer Treatments
Product News

BioAscent Collaborates To Identify Potential Cancer Treatments

BioAscent Collaborates To Identify Potential Cancer Treatments
Product News

BioAscent Collaborates To Identify Potential Cancer Treatments


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BioAscent scientists, working in collaboration with teams at the German Cancer Research Center and the Pivot Park Screening Centre as part of the European Lead Factory project, have helped to discover potent and selective inhibitors of enzymes associated with the development of some cancers and neurodegenerative diseases. The findings, published in ChemMedChem, represent an initial step in the development of potential new cancer treatments.

The German Cancer Research Center (DKFZ) is the largest biomedical research institute in Germany with over 1,200 scientists in over 90 divisions and research groups working on cancer research. As part of their research, one of the DKFZ teams proposed a role for Kallikrein-related peptidase 6 (KLK6) in the development, invasiveness and metastasis of some cancers, including colon cancer and melanomas. Having suggested this biological pathway, they wanted to identify compounds that inhibited KLK6 activity in order to test their hypothesis and identify starting points for a drug discovery project.   

After an initial high throughput screen performed by the Pivot Park Screening Centre had identified a cluster of initial hits that showed consistent inhibitory activity against KLK6, the hits were validated and improved by a team of biologists and chemists, who have since transitioned to BioAscent. Using their expertise in medicinal and synthetic chemistry, novel chiral compounds were efficiently prepared using multi-step synthesis procedures and tested using a range of biophysical and biochemical assays.

Using an iterative and rational design-make-test approach driven by structure-guided design, the team rapidly developed highly effective chemical leads against KLK6, with single digit nanomolar potency and good to excellent selectivity. Subsequent profiling found that one of these compounds reduced the invasion of colon cancer (HCT116) cells in a dose-dependent manner. 

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