Version 1
: Received: 11 June 2024 / Approved: 12 June 2024 / Online: 12 June 2024 (11:58:34 CEST)
How to cite:
Sinanian, M. M.; Rahman, A.; Elshazly, A. M.; Neely, V. L.; Nagarajan, B.; Kellogg, G. E.; Risinger, A. L.; Gewirtz, D. A. A Bptf Inhibitor That Interferes with the Multidrug Resistance Pump to Sensitize Triple Negative Breast Cancer Cells to Chemotherapy. Preprints2024, 2024060791. https://doi.org/10.20944/preprints202406.0791.v1
Sinanian, M. M.; Rahman, A.; Elshazly, A. M.; Neely, V. L.; Nagarajan, B.; Kellogg, G. E.; Risinger, A. L.; Gewirtz, D. A. A Bptf Inhibitor That Interferes with the Multidrug Resistance Pump to Sensitize Triple Negative Breast Cancer Cells to Chemotherapy. Preprints 2024, 2024060791. https://doi.org/10.20944/preprints202406.0791.v1
Sinanian, M. M.; Rahman, A.; Elshazly, A. M.; Neely, V. L.; Nagarajan, B.; Kellogg, G. E.; Risinger, A. L.; Gewirtz, D. A. A Bptf Inhibitor That Interferes with the Multidrug Resistance Pump to Sensitize Triple Negative Breast Cancer Cells to Chemotherapy. Preprints2024, 2024060791. https://doi.org/10.20944/preprints202406.0791.v1
APA Style
Sinanian, M. M., Rahman, A., Elshazly, A. M., Neely, V. L., Nagarajan, B., Kellogg, G. E., Risinger, A. L., & Gewirtz, D. A. (2024). A Bptf Inhibitor That Interferes with the Multidrug Resistance Pump to Sensitize Triple Negative Breast Cancer Cells to Chemotherapy. Preprints. https://doi.org/10.20944/preprints202406.0791.v1
Chicago/Turabian Style
Sinanian, M. M., April L. Risinger and David A. Gewirtz. 2024 "A Bptf Inhibitor That Interferes with the Multidrug Resistance Pump to Sensitize Triple Negative Breast Cancer Cells to Chemotherapy" Preprints. https://doi.org/10.20944/preprints202406.0791.v1
Abstract
Triple negative breast cancer (TNBC) is associated with a generally poor prognosis due to its highly aggressive and metastatic nature, lack of targetable receptors, as well as the frequent development of resistance to chemotherapy. We previously reported that AU1, a small molecule developed as an inhibitor of BPTF (bromodomain PHD finger containing transcription factor), was capable of sensitizing preclinical models of triple negative breast cancer to chemotherapy, in part via the promotion of autophagy. In studies reported here, we identify an additional property of this compound, specifically that sensitization is associated with inhibition of the P-glycoprotein efflux pump. In silico molecular docking studies indicate that AU1 binds to active regions of the efflux pump, in a manner consistent with inhibition of pump function. This work identifies a novel chemical structure that can influence multidrug efflux, an established mechanism of drug resistance in triple negative breast cancer, that has not yet been successfully addressed by clinical efforts.
Keywords
p-gp; p-glycoprotein; AU1; BPTF inhibitor; triple negative breast cancer; efflux pump; multidrug resistance; multidrug resistance pump; breast cancer
Subject
Biology and Life Sciences, Biochemistry and Molecular Biology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
,
,
,
,
