05 Sep TUMAGNOSTIC – Three key academic publications on CP-506
Several academic centers have collaborated with Convert Pharmaceuticals to expand knowledge about its main compound, CP-506, and the biomarkers that will enable selection of patients that would most benefit from the hypoxia activated prodrug under investigation. These research efforts have recently led to three key peer-reviewed academic publications which are referenced here-under.
The results from the first paper1, published in 2021, demonstrate that CP-506 selectively targets hypoxic tumor cells and has broad antitumor activity.
The second paper2, published in 2022, focusses on the in vivo identification of Adducts from CP-506. The resulting in vitro data suggests that the structural changes performed on CP-506 improved the drug selectivity toward hypoxic conditions compared to its predecessor PR-104, as shown by more adducts being detected in anoxic versus normoxic treatment, but did not completely eliminate its ability to react directly with DNA enabling a bystander-effect.
This favorable bystander efficiency of the new generation pro-drug has been further studied using in silico spatially-resolved pharmacokinetic/pharmacodynamic (SR-PK/PD) modelling and spheroid co-cultures for validation. The results of this study, demonstrating the favourable pharmacological properties of CP-506 in tumour tissue, have been published in a third recently published paper3.
1 van der Wiel, A. M. A., Jackson-Patel, V., Niemans, R., Yaromina, A., Liu, E., Marcus, D., … Lambin, P. (2021). Selectively Targeting Tumor Hypoxia With the Hypoxia-Activated Prodrug CP-506. Molecular Cancer Therapeutics, 20(12), 2372-2383. https://doi.org/10.1158/1535-7163.MCT-21-0406
2 Solivio, M. J., Stornetta, A., Gilissen, J., Villalta, P. W., Deschoemaeker, S., Heyerick, A., … Balbo, S. (2022). In Vivo Identification of Adducts from the New Hypoxia-Activated Prodrug CP-506 Using DNA Adductomics. Chemical Research in Toxicology, 35. https://doi.org/10.1021/acs.chemrestox.1c00329
3 Jackson-Patel, V., Liu, E., Bull, M. R., Ashoorzadeh, A., Bogle, G., Wolfram, A., Hicks, K. O., Smaill, J. B., & Patterson, A. V. (2022). Tissue Pharmacokinetic Properties and Bystander Potential of Hypoxia-Activated Prodrug CP-506 by Agent-Based Modelling. Frontiers in pharmacology, 13, 803602. https://doi.org/10.3389/fphar.2022.803602