A team of Polish scientists has developed and tested a new chemical compound, DK-AT390HCl, which exhibits strong anti-cancer activity against colorectal cancer (CRC) cells, while having a limited effect on healthy tissues.
The research was conducted in collaboration with scientists from the Cracow University of Technology, the Hugo Kołłątaj University of Agriculture in Krakow, and the Ludwik Hirszfeld Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences, which carried out key in vitro and in vivo biological studies evaluating the anti-cancer activity of the compound.
The DK-AT390HCl compound was selected from over 200 newly designed and synthesised molecules. Initially, it was tested for its activity against triple-negative breast cancer, but further analyses showed its particularly strong and selective effect on colon cancer cells, with minimal damage to healthy cells.
One of the mechanisms of action of DK-AT390HCl is the inhibition of autophagy in cancer cells – a process that enables them to survive in unfavourable conditions, including during chemotherapy. Blocking this mechanism can significantly increase the effectiveness of cancer therapy, especially in cancers with KRAS or BRAF mutations.
The research included cytotoxicity tests, colony formation tests, assessment of cancer cell migration, determination of the maximum tolerated dose (MTD), assessment of the effect on tumour mass, and molecular studies of cancer tissue. The results indicate the compound’s high potential as a candidate for further therapeutic development.
The biological research conducted at the Institute of Immunology and Experimental Therapy of the Polish Academy of Sciences involved, among others, Aleksandra Strzykalska-Augustyniak, PhD, and Beata Filip-Psurska, PhD, Eng, from the Laboratory of Experimental Anticancer Therapy, as well as Michalina Gos, MSc, from the Laboratory of Biomedical Chemistry.
The work carried out so far has resulted in four patent applications concerning the anti-cancer activity of the DK-AT390HCl compound and its derivatives. The commercialisation of the results in cooperation with a partner from the pharmaceutical industry is being considered.
The research was carried out as part of projects financed by the National Centre for Research and Development LIDER XII programme and European Funds for Modern Economy (FENG). The research team is led by Damian Kułaga, PhD, Eng, from the Cracow University of Technology.