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BIOTEK2021-Bioteknologi for verdiskaping

KOMM: Tackling drug resistant acute myeloid leukaemia with the next-generation FLT3 inhibitor

Alternative title: Kinasehemmere mot blodkreft (TackAML)

Awarded: NOK 8.0 mill.

We have discovered a family of novel natural products from a sessile, bottom-living Arctic marine animal, and these compounds were found to inhibit the survival of selected cancer cell lines. After further examination, this activity was shown to be caused by inhibition of kinases. Kinases are key regulators of many biological processes, including cell division, and in many types of cancer kinases are over-expressed or over-active. By targeting specific types of cancers with kinase inhibitors, it is possible to stop uncontrolled cell division of cancer cells without affecting normal cells. The scaffold of the natural products we isolated from the marine animal was used as a starting point for production of synthetic analogues. We have now developed a new set of kinase inhibitors that are more potent and selective, but less toxic compared to the original natural products. We can now target just one specific type of blood cancer by inhibiting a specific mutated variant of a kinase, which is the cause of cancer in ~30% of these patients. In addition, some of the new variants have favourable drug-like properties, indicating that that they are well suited to be used by humans. Through this project we have produced new analogues with further improved drug-likeness of our front-running compounds. This include improved metabolic stability in order to prevent that the kinase inhibitors are removed from the body before they reach the cancer cells. At the end of this project we will test the most promising molecules in a mouse model. Achieved compounds with confirmed stability in vivo.

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Funding scheme:

BIOTEK2021-Bioteknologi for verdiskaping