Researchers from Pavlína Řezáčová Group at IOCB Prague in extensive collaboration with scientists from the Institute of Inorganic Chemistry of the CAS, Institute of Molecular and Translational Medicine, and Institute of Molecular Genetics of the CAS synthesized and tested a novel class of anticancer agents based on carborane cobalt complexes.
Their action is based on inhibition of CAIX, a protein commonly found in hypoxic tumor tissues, while its expression in normal tissues is vanishingly low. The best-performing molecules of this class exhibit remarkable selectivity towards this enzyme over its isoform CAII commonly found in normal tissues.
Tests performed in vitro as well as on mice show significant tumor size reduction, favorable pharmacological properties of the molecules, and a synergistic effect with a known and used chemotherapeutic DOX.
Read the paper:
- Grüner, B.; Brynda, J.; Das, V.; Šícha, V.; Štěpánková, J.; Nekvinda, J.; Holub, J.; Pospíšilová, K.; Fábry, M.; Pachl, P.; Král, V.; Kugler, M.; Mašek, V.; Medvedíková, M.; Matějková, S.; Nová, A.; Lišková, B.; Gurská, S.; Džubák, P.; Hajdúch, M.; Řezáčová, P. Metallacarborane Sulfamides: Unconventional, Specific, and Highly Selective Inhibitors of Carbonic Anhydrase IX. Journal of Medicinal Chemistry 2019, 62, 9560-9575. https://doi.org/10.1021/acs.jmedchem.9b00945
