Does the Glandular Tolerant to McL-1 Inhibitor S63845?
DOI:
https://doi.org/10.61173/5sd16q58Abstract
MCL-1 is an anti-apoptotic protein that regulates cell apoptosis and has been observed in over-expression in many
cancer. It makes the MCL-1 an available target. S63845 is introduced to treat cancer, an inhibitor with a high affinity to
MCL-1. However, the tolerability of the human body to the treatment remains unanswered. Therefore in this paper, we
designed the experiment to test the tolerability of regular issue glandular with cancerous individuals of the same cell
line, the apoptosis will be tested by the MTT theory, and the direct production of inhibition --BAX will be measured
by western blot. The result is predicted, and this work will provide meaningful information for future cancer treatment.
Future studies should focus on cooperation with other BCL-2 inhibitors and the impact of the treatment.
References
[1] Colon and Rectal Cancer https://www.cancerquest.org/ patients/cancer-type/colon-and-rectal-cancer on 10/01/2022 Colon cancer and rectal cancer, collectively known as colorectal cancer, have man Colon and Rectal Cancer | CancerQuest
[2] Wang H, Guo M, Wei H, Chen Y. Targeting MCL-1 in cancer: current status and perspectives. J Hematol Oncol. 2021 Apr 21;14(1):67. doi: 10.1186/s13045-021-01079-1. PMID: 33883020; PMCID: PMC8061042.
[3] Algarín EM, Quwaider D, Campos-Laborie FJ, Díaz-Tejedor A, Mogollón P, Vuelta E, Martín-Sánchez M, San-Segundo L, González-Méndez L, Gutiérrez NC, García-Sanz R, Paíno T, De Las Rivas J, Ocio EM, Garayoa M. Stroma-Mediated Resistance to S63845 and Venetoclax through MCL-1 and BCL-2 Expression Changes Induced by miR-193b-3p and miR- 21-5p Dysregulation in Multiple Myeloma. Cells. 2021 Mar 4;10(3):559. doi: 10.3390/cells10030559. PMID: 33806619; PMCID: PMC8001939.
[4] Kotschy, A., Szlavik, Z., Murray, J. et al. The MCL1 inhibitor S63845 is tolerable and effective in diverse cancer models. Nature 538, 477–482 (2016). https://doi.org/10.1038/ nature19830
[5] Xiang W, Yang CY, Bai L. MCL-1 inhibition in cancer treatment. Onco Targets Ther. 2018 Oct 23;11:7301-7314. doi: 10.2147/OTT.S146228. PMID: 30425521; PMCID: PMC6205821.
[6] Pan R, Hogdal LJ, Benito JM, Bucci D, Han L, Borthakur G, Cortes J, DeAngelo DJ, Debose L, Mu H, Döhner H, Gaidzik VI, Galinsky I, Golfman LS, Haferlach T, Harutyunyan KG, Hu J, Leverson JD, Marcucci G, Müschen M, Newman R, Park E, Ruvolo PP, Ruvolo V, Ryan J, Schindela S, Zweidler-McKay P, Stone RM, Kantarjian H, Andreeff M, Konopleva M, Letai AG. Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia. Cancer Discov. 2014 Mar;4(3):362-75. doi: 10.1158/2159-8290.CD-13-0609. Epub 2013 Dec 17. PMID: 24346116; PMCID: PMC3975047.
[7] Kumar P, Nagarajan A, Uchil PD. Analysis of Cell Viability by the MTT Assay. Cold Spring Harb Protoc. 2018 Jun 1;2018(6). doi: 10.1101/pdb.prot095505. PMID: 29858338.
[8] Taylor SC, Posch A. The design of a quantitative western blot experiment. Biomed Res Int. 2014;2014:361590. doi: 10.1155/2014/361590. Epub 2014 Mar 16. PMID: 24738055; Dean&Francis PMCID: PMC3971489.
[9] Leverson, J., Zhang, H., Chen, J. et al. Potent and selective small-molecule MCL-1 inhibitors demonstrate on-target cancer cell killing activity as single agents and in combination with ABT-263 (navitoclax). Cell Death Dis 6, e1590 (2015). https:// doi.org/10.1038/cddis.2014.561
[10] Pan R, Hogdal LJ, Benito JM, Bucci D, Han L, Borthakur G, Cortes J, DeAngelo DJ, Debose L, Mu H, Döhner H, Gaidzik VI, Galinsky I, Golfman LS, Haferlach T, Harutyunyan KG, Hu J, Leverson JD, Marcucci G, Müschen M, Newman R, Park E, Ruvolo PP, Ruvolo V, Ryan J, Schindela S, Zweidler-McKay P, Stone RM, Kantarjian H, Andreeff M, Konopleva M, Letai AG. Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia. Cancer Discov. 2014 Mar;4(3):362-75. doi: 10.1158/2159-8290.CD-13-0609. Epub 2013 Dec 17. PMID: 24346116; PMCID: PMC3975047.
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