Berubicin: Anthracyclines inhibit the topoisomerase II enzyme to disrupt DNA and RNA synthesis by intercalating between base pairs of the DNA/RNA strand, thus preventing the replication of rapidly growing cancer cells.

Anthracyclines

Furthermore, anthracyclines inhibit the topoisomerase II enzyme, preventing relaxation of supercoiled DNA, thus blocking DNA transcription and replication. However, all previously studied anthracyclines are hampered due to their inability to cross the blood-brain-barrier, limiting their effectiveness to treat tumors in the brain.

One of the most important mechanisms of maintaining the blood-brain barrier are the multidrug resistance proteins that result in drug efflux.  Berubicin was designed from the conserved doxorubicin molecular structure and is tailor-made to improve lipophilicity by the addition of a 4’-O-benzyl substituent covalently bound to the anthracycline glycone ring. Its ability to circumvent ATP-binding cassette transporters, Multidrug Resistant Protein-1 (MRP1), P-glycoprotein (P-gp), and to penetrate the blood-brain barrier differentiates it from other clinically available anthracyclines.

Berubicin

Berubicin is a topoisomerase II inhibitor like other anthracyclines. With IC50 values in the mid-nanomolar range, Berubicin was observed to be more potent than doxorubicin in vitro.1 Among pairs of non-resistant and resistant cell lines, Berubicin demonstrated a resistance index at least 10-fold less than doxorubicin. 

Tumor cells also have multidrug resistance proteins that develop after exposure to chemotherapy and which mediate tumor resistance due to the  expression of these drug efflux pumps.

Publications and Presentations

11 August, 2023 2023 SNO/ASCO CNS Cancer Conference
A Randomized, Controlled Trial Of Berbubicin, A Novel Topoisomerase II Inhibitor, After First-Line Therapy For Glioblastoma Multiforme (GBM): Updated Results
By: Z. Muzyczenko (1), S. Silberman (1), S. Hsu (2), D. Picker (1) (1) CNS Pharmaceuticals, Houston, TX, (2) Memorial Hermann Texas Medical Center, Houston, TX,
Download A Randomized, Controlled Trial Of Berbubicin, A Novel Topoisomerase II Inhibitor, After First-Line Therapy For Glioblastoma Multiforme (GBM): Updated Results PDF
18 November, 2022 Society for Neuro-Oncology Annual Meeting 2022
A Randomized, Controlled Trial Of Berbubicin, A Novel Topoisomerase II Inhibitor, After First-Line Therapy For Glioblastoma Multiforme (GBM): Preliminary Results
By: S. Silberman (1), S. Hsu (2), Z. Muzyczenko (1), D. Picker (1), S. Bisdas (3), O. Kubassova (4), J. O‘Lynn (4), W. Priebe (5) (1) CNS Pharmaceuticals, Houston, TX, (2) Memorial Hermann Texas Medical Center, Houston, TX, (3) UCL Hospitals NHS Trust, London, UK, (4) IAG, Image Analysis Group, London, UK, (5) MD Anderson Cancer Center, Houston, TX
Download A Randomized, Controlled Trial Of Berbubicin, A Novel Topoisomerase II Inhibitor, After First-Line Therapy For Glioblastoma Multiforme (GBM): Preliminary Results PDF
05 June, 2022 American Society of Clinical Oncology Annual Meeting 2022
Design And Initiation Of An Adaptive, Randomized, Controlled Study Of Berubicin, A Topoisomerase II Poison That Crosses The Blood-Brain Barrier For The Treatment Of Recurrent Glioblastoma Multiforme (GBM)
By: S. Silberman (1), S. Hsu (2), Z. Muzyczenko (1), D. Picker (1), W. Priebe (3) (1) CNS Pharmaceuticals, Houston, TX, (2) Memorial Hermann Texas Medical Center, Houston, TX, (3) The University of Texas M. D. Anderson Cancer Center, Houston, TX
Download Design And Initiation Of An Adaptive, Randomized, Controlled Study Of Berubicin, A Topoisomerase II Poison That Crosses The Blood-Brain Barrier For The Treatment Of Recurrent Glioblastoma Multiforme (GBM) PDF
19 November, 2021 Society for Neuro-Oncology Annual Meeting 2021
Design and Initiation Of Pivotal Studies For Berubicin, A Novel, Potent Topoisomerase II Poison For The Treatment Of Recurrent Glioblastoma Multiforme (GBM)
By: S. Silberman (1), S. Hsu (2), Z. Muczyczenko (1), D. Picker (1), M. Sipowicz (3), E. Żak (3), A. Buczyńska (3), M. Olejniczak (3), W. Priebe (4) (1) CNS Pharmaceuticals, Houston, TX, (2) Memorial Hermann Texas Medical Center, Houston, TX, (3) WPD Pharmaceuticals, Warszawa, Poland, (4) The University of Texas M. D. Anderson Cancer Center, Houston, TX
Download Design and Initiation Of Pivotal Studies For Berubicin, A Novel, Potent Topoisomerase II Poison For The Treatment Of Recurrent Glioblastoma Multiforme (GBM) PDF

References

  • 1. Zielinski, R., Cardenas-Zuniga, R., Poimenidou M., et al. Neuro-Oncol. 2021; 23 (6):1