E-OxidoCurin Targets and biomarkers of the novel anticancer compounds inducing oxidative stress in cancer cells
Reference number | |
Coordinator | HDxperts AB |
Funding from Vinnova | SEK 4 888 259 |
Project duration | October 2017 - December 2021 |
Status | Completed |
Venture | Eurostars |
Purpose and goal
All the goals of the project were fulfilled. 1) A new water-soluble lead compound LCTA2940 was synthesized. 2) The TrxR1 target was validated, and the mechanism of interaction and ROS dependent action was elucidated. 3) Using proteomics, we identified additional targets. 4) In vivo LCTA2940 effectively suppressed the growth of xenograft tumors without side effects. 5) Bioinformatics analysis of sensitivity profiles of 27 cancer cell lines identified biomarkers for compounds efficacy and possible toxicity.
Expected results and effects
Our novel anti-cancer compound LCTA2940 has an exceptional set of pharmacological properties such as significant tumor suppression in animal models in vivo, along with no damage in DNA and little effect on normal cells. The mechanism of action of LCTA2940 involves the induction of ROS via targeting TrxR1. LCTA2940 has increased efficiency in hypoxic cells, which are the most aggressive types of cancer. We also have shown that the compound LCTA2940 kills cancer stem cells, which reduces the risk of recurrence and reduces the likelihood of treatment resistance.
Planned approach and implementation
1) A new water-soluble lead compound LCTA2940 was synthesized. 2) The TrxR1 target was validated, and the mechanism of interaction and ROS dependent action was elucidated. 3) Using proteomics, we identified additional targets. 4) In vivo LCTA2940 effectively suppressed the growth of xenograft tumors without side effects. 5) Bioinformatics analysis of sensitivity profiles of 27 cancer cell lines identified biomarkers for compounds efficacy and possible toxicity. The goals of the project has been fulfilled.