Derleme
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Kanser Tedavisinde Yeni Bir Yaklaşım “Proteoliz Hedefli Kimera”

Yıl 2023, Cilt: 6 Sayı: 2, 1611 - 1640, 05.07.2023

Öz

Gelişmekte olan terapötik bir strateji olarak Proteoliz Hedefli Kimera (PROTAC), belirli bir hedef protein aktivitesinin inhibisyonundan ziyade, degredasyonuna yol açan iki işlevli bir moleküldür. PROTAC molekülleri, bir hedef protein ligandı, E3 ligaz ve bir bağlayıcı olmak üzere üç kısımdan oluşmakta ve farklı hedef proteinleri parçalamak için hücredeki ubikutin proteozom sistemini kullanmaktadır. PROTAC teknolojisi, son yirmi yılda önemli ölçüde ilerlemiş ve günümüzde de dikkatleri üzerinde toplayarak kanser tedavisinde çığır açabilecek bir dönüm noktası haline gelmiştir. PROTAC yaklaşımı aynı zamanda ilaç keşif çalışmalarında yıkıcı bir değişikliğe sebep olmakla birlikte bu teknolojinin önünde yatan birçok potansiyel avantaj ve olağanüstü zorluklar tartışılmaktadır. Bu derlemede, PROTAC’ın geleneksel ve modern tedavi yöntemleri ile karşılaştırılarak, kanser tedavisine ve ilaç keşif çalışmalarına katkı sağlayacak avantaj ve zorluklarına yönelik bilgilere yer verilmektedir.

Destekleyen Kurum

Bingöl Üniversitesi

Kaynakça

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Proteolysis Targeted Chimera “PROTAC”

Yıl 2023, Cilt: 6 Sayı: 2, 1611 - 1640, 05.07.2023

Öz

As an emerging therapeutic strategy, Proteolysis Targeted Chimera (PROTAC) is a bifunctional molecule that leads to degradation rather than inhibition of the activity of a specific target protein. PROTAC molecules consist of three parts, a target protein ligand, E3 ligase, and a linker, and use the ubiquitin proteosome system in the cell to cleave different target proteins. PROTAC technology has advanced significantly in the last two decades and has become a breakthrough in cancer treatment by attracting attention today. While the PROTAC approach is also causing a devastating change in drug discovery studies, the many potential advantages and extraordinary challenges that lie ahead of this technology are discussed. In this review, information on the advantages and challenges of PROTAC that will contribute to cancer treatment and drug discovery studies is given by comparing it with traditional and modern treatment methods.

Kaynakça

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  • Morán Luengo, T., Mayer, M. P., & Rüdiger, S. G. D. (2019). The Hsp70–Hsp90 Chaperone Cascade in Protein Folding. Trends in Cell Biology, 29(2), 164–177. https://doi.org/10.1016/j.tcb.2018.10.004
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  • Nalawansha, D. A., & Crews, C. M. (2020). PROTACs: An Emerging Therapeutic Modality in Precision Medicine. Cell Chemical Biology, 27(8), 998–1014. https://doi.org/10.1016/j.chembiol.2020.07.020
  • Neklesa, T. K., Winkler, J. D., & Crews, C. M. (2017). Targeted protein degradation by PROTACs. Pharmacology and Therapeutics, 174, 138–144. https://doi.org/10.1016/j.pharmthera.2017.02.027
  • Neklesa, T., Snyder, L. B., Willard, R. R., Vitale, N., Pizzano, J., Gordon, D. A., Bookbinder, M., Macaluso, J., Dong, H., Ferraro, C., Wang, G., Wang, J., Crews, C. M., Houston, J., Crew, A. P., & Taylor, I. (2019). ARV-110: An oral androgen receptor PROTAC degrader for prostate cancer. Journal of Clinical Oncology, 37(7_suppl), 259–259. https://doi.org/10.1200/jco.2019.37.7_suppl.259
  • Nguyen, T. T. L., Kim, J. W., Choi, H. I., Maeng, H. J., & Koo, T. S. (2022). Development of an LC-MS/MS Method for ARV-110, a PROTAC Molecule, and Applications to Pharmacokinetic Studies. Molecules, 27(6). https://doi.org/10.3390/molecules27061977
  • Ocaña, A., & Pandiella, A. (2020). Proteólisis dirigida a quimeras (PROTACs) en la terapia del cáncer. Revista de Investigación Experimental y Clínica Del Cáncer, 39(1), 2–9. https://pubmed.ncbi.nlm.nih.gov/32933565/%0Ahttps://t.ly/TJaC
  • Paiva, S. L., & Crews, C. M. (2019). Targeted protein degradation: elements of PROTAC design. Current Opinion in Chemical Biology, 50, 111–119. https://doi.org/10.1016/j.cbpa.2019.02.022
  • Park, J., Cho, J., & Song, E. J. (2020). Ubiquitin–proteasome system (UPS) as a target for anticancer treatment. Archives of Pharmacal Research, 43(11), 1144–1161. https://doi.org/10.1007/s12272-020-01281-8
  • Pietri, E., Conteduca, V., Andreis, D., Massa, I., Melegari, E., Sarti, S., Cecconetto, L., Schirone, A., Bravaccini, S., Serra, P., Fedeli, A., Maltoni, R., Amadori, D., De Giorgi, U., & Rocca, A. (2016). Androgen receptor signaling pathways as a target for breast cancer treatment. Endocrine-Related Cancer, 23(10), R485–R498. https://doi.org/10.1530/ERC-16-0190
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  • Pu, L., Govindaraj, R. G., Lemoine, J. M., Wu, H. C., & Brylinski, M. (2019). Deepdrug3D: Classification of ligand-binding pockets in proteins with a convolutional neural network. PLoS Computational Biology, 15(2), 1–23. https://doi.org/10.1371/journal.pcbi.1006718
  • Qu, X., Liu, H., Song, X., Sun, N., Zhong, H., Qiu, X., Yang, X., & Jiang, B. (2021). Effective degradation of EGFRL858R+T790M mutant proteins by CRBN-based PROTACs through both proteosome and autophagy/lysosome degradation systems. European Journal of Medicinal Chemistry, 218, 113328. https://doi.org/10.1016/j.ejmech.2021.113328
  • Radchikov, V. F., Besarab, G. V., Sapsaleva, T. L., Baranikov, V. A., Glushenko, A. V., & Spivak, M. E. (2021). Rationing of non-degradable protein in diets for breeding steers. IOP Conference Series: Earth and Environmental Science, 848(1). https://doi.org/10.1088/1755-1315/848/1/012079
  • Raina, K., Lu, J., Qian, Y., Altieri, M., Gordon, D., Rossi, A. M. K., Wang, J., Chen, X., Dong, H., Siu, K., Winkler, J. D., Crew, A. P., Crews, C. M., & Coleman, K. G. (2016). PROTAC-induced BET protein degradation as a therapy for castration-resistant prostate cancer. Proceedings of the National Academy of Sciences of the United States of America, 113(26), 7124–7129. https://doi.org/10.1073/pnas.1521738113
  • Rashighi, M., & Harris, J. E. (2017). HHS Public Access. Physiology & Behavior, 176(3), 139–148. https://doi.org/10.1016/j.ddtec.2019.01.002.PROteolysis
  • Rathod, D., Fu, Y., & Patel, K. (2019). BRD4 PROTAC as a novel therapeutic approach for the treatment of vemurafenib resistant melanoma: Preformulation studies, formulation development and in vitro evaluation. European Journal of Pharmaceutical Sciences, 138(July), 105039. https://doi.org/10.1016/j.ejps.2019.105039
  • Relini, A., Marano, N., & Gliozzi, A. (2014). Misfolding of amyloidogenic proteins and their interactions with membranes. Biomolecules, 4(1), 20–55. https://doi.org/10.3390/biom4010020
  • Roskoski, R. (2017). Anaplastic lymphoma kinase (ALK) inhibitors in the treatment of ALK-driven lung cancers. Pharmacological Research, 117, 343–356. https://doi.org/10.1016/j.phrs.2017.01.007
  • Saeki, Y., Tanaka, K., Wijk, S. J. L. Van, Bienko, M., Dikic, I., Lysine, M., Besche, H. C., Goldberg, A. L., & Kim, H. T. (2012). Ubiquitin Family Modifiers and the Proteasome. Methods in Molecular Biology, 832(1), 423–432. https://doi.org/10.1007/978-1-61779-474-2
  • Sakamoto, K. M. (2010). Protacs for treatment of cancer. Pediatric Research, 67(5), 505–508. https://doi.org/10.1203/PDR.0b013e3181d35017
  • Sakamoto, K. M., Kim, K. B., Kumagai, A., Mercurio, F., Crews, C. M., & Deshaies, R. J. (2001). Protacs: Chimeric molecules that target proteins to the Skp1-Cullin-F box complex for ubiquitination and degradation. Proceedings of the National Academy of Sciences of the United States of America, 98(15), 8554–8559. https://doi.org/10.1073/pnas.141230798
  • Sakamoto, K. M., Kim, K. B., Verma, R., Ransick, A., Stein, B., Crews, C. M., & Deshaies, R. J. (2003). Development of Protacs to target cancer-promoting proteins for ubiquitination and degradation. Molecular & Cellular Proteomics : MCP, 2(12), 1350–1358. https://doi.org/10.1074/mcp.T300009-MCP200
  • Samarasinghe, K. T. G., & Crews, C. M. (2021). Targeted protein degradation: A promise for undruggable proteins. Cell Chemical Biology, 28(7), 934–951. https://doi.org/10.1016/j.chembiol.2021.04.011
  • Savvidou, M. G., Katsabea, A., Kotidis, P., Mamma, D., Lymperopoulou, T. V., Kekos, D., & Kolisis, F. N. (2018). Studies on the catalytic behavior of a membrane-bound lipolytic enzyme from the microalgae Nannochloropsis oceanica CCMP1779. Enzyme and Microbial Technology, 116, 64–71. https://doi.org/10.1016/j.enzmictec.2018.05.011
  • Schneekloth, J. S., Fonseca, F. N., Koldobskiy, M., Mandal, A., Deshaies, R., Sakamoto, K., & Crews, C. M. (2004). Chemical Genetic Control of Protein Levels: Selective in Vivo Targeted Degradation. Journal of the American Chemical Society, 126(12), 3748–3754. https://doi.org/10.1021/ja039025z
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  • Sun, X., Gao, H., Yang, Y., He, M., Wu, Y., Song, Y., Tong, Y., & Rao, Y. (2019). Protacs: Great opportunities for academia and industry. Signal Transduction and Targeted Therapy, 4(1). https://doi.org/10.1038/s41392-019-0101-6
  • Sun, Y., Zhao, X., Ding, N., Gao, H., Wu, Y., Yang, Y., Zhao, M., Hwang, J., Song, Y., Liu, W., & Rao, Y. (2018). PROTAC-induced BTK degradation as a novel therapy for mutated BTK C481S induced ibrutinib-resistant B-cell malignancies. Cell Research, 28(7), 779–781. https://doi.org/10.1038/s41422-018-0055-1
  • Tang, K., Jia, Y. N., Yu, B., & Liu, H. M. (2020). Medicinal chemistry strategies for the development of protein tyrosine phosphatase SHP2 inhibitors and PROTAC degraders. European Journal of Medicinal Chemistry, 204, 112657. https://doi.org/10.1016/j.ejmech.2020.112657
  • Tinworth, C. P., Lithgow, H., Dittus, L., Bassi, Z. I., Hughes, S. E., Muelbaier, M., Dai, H., Smith, I. E. D., Kerr, W. J., Burley, G. A., Bantscheff, M., & Harling, J. D. (2019). PROTAC-Mediated Degradation of Bruton’s Tyrosine Kinase Is Inhibited by Covalent Binding. ACS Chemical Biology, 14(3), 342–347. https://doi.org/10.1021/acschembio.8b01094
  • Toure, M., & Crews, C. M. (2016). Small-molecule PROTACS: New approaches to protein degradation. Angewandte Chemie - International Edition, 55(6), 1966–1973. https://doi.org/10.1002/anie.201507978
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  • Zeng, S., Huang, W., Zheng, X., Liyan cheng, Zhang, Z., Wang, J., & Shen, Z. (2021). Proteolysis targeting chimera (PROTAC) in drug discovery paradigm: Recent progress and future challenges. European Journal of Medicinal Chemistry, 210, 112981. https://doi.org/10.1016/j.ejmech.2020.112981
  • Zhang. (2004). Targeted Degradation of Proteins by Small Molecules: A Novel Tool for Functional Proteomics†. Combinatorial Chemistry & High Throughput Screening, 7(7), 689–697. https://doi.org/10.2174/1386207043328364 Zhang, H., Zhao, H. Y., Xi, X. X., Liu, Y. J., Xin, M., Mao, S., Zhang, J. J., Lu, A. X., & Zhang, S. Q. (2020). Discovery of potent epidermal growth factor receptor (EGFR) degraders by proteolysis targeting chimera (PROTAC). European Journal of Medicinal Chemistry, 189, 112061. https://doi.org/10.1016/j.ejmech.2020.112061
  • Zhao, L., Han, X., Lu, J., McEachern, D., & Wang, S. (2020). A highly potent PROTAC androgen receptor (AR) degrader ARD-61 effectively inhibits AR-positive breast cancer cell growth in vitro and tumor growth in vivo. Neoplasia (United States), 22(10), 522–532. https://doi.org/10.1016/j.neo.2020.07.002
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  • Zhou, X., Dong, R., Zhang, J. Y., Zheng, X., & Sun, L. P. (2020). PROTAC: A promising technology for cancer treatment. European Journal of Medicinal Chemistry, 203, 112539. https://doi.org/10.1016/j.ejmech.2020.112539
  • Zhuang, J. jing, Liu, Q., Wu, D. lei, & Tie, L. (2022). Current strategies and progress for targeting the “undruggable” transcription factors. Acta Pharmacologica Sinica, December 2021, 1–8. https://doi.org/10.1038/s41401-021-00852-9 Zou, Y., Ma, D., & Wang, Y. (2019). The PROTAC technology in drug development. Cell Biochemistry and Function, 37(1), 21–30. https://doi.org/10.1002/cbf.3369 20050415 053. (2004).
Toplam 104 adet kaynakça vardır.

Ayrıntılar

Birincil Dil Türkçe
Bölüm Derlemeler (REVIEWS)
Yazarlar

Seher Saruhan

Can Ali Agca

Yayımlanma Tarihi 5 Temmuz 2023
Gönderilme Tarihi 16 Haziran 2022
Kabul Tarihi 20 Ekim 2022
Yayımlandığı Sayı Yıl 2023 Cilt: 6 Sayı: 2

Kaynak Göster

APA Saruhan, S., & Agca, C. A. (2023). Kanser Tedavisinde Yeni Bir Yaklaşım “Proteoliz Hedefli Kimera”. Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 6(2), 1611-1640.
AMA Saruhan S, Agca CA. Kanser Tedavisinde Yeni Bir Yaklaşım “Proteoliz Hedefli Kimera”. OKÜ Fen Bil. Ens. Dergisi ((OKU Journal of Nat. & App. Sci). Temmuz 2023;6(2):1611-1640.
Chicago Saruhan, Seher, ve Can Ali Agca. “Kanser Tedavisinde Yeni Bir Yaklaşım ‘Proteoliz Hedefli Kimera’”. Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi 6, sy. 2 (Temmuz 2023): 1611-40.
EndNote Saruhan S, Agca CA (01 Temmuz 2023) Kanser Tedavisinde Yeni Bir Yaklaşım “Proteoliz Hedefli Kimera”. Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi 6 2 1611–1640.
IEEE S. Saruhan ve C. A. Agca, “Kanser Tedavisinde Yeni Bir Yaklaşım ‘Proteoliz Hedefli Kimera’”, OKÜ Fen Bil. Ens. Dergisi ((OKU Journal of Nat. & App. Sci), c. 6, sy. 2, ss. 1611–1640, 2023.
ISNAD Saruhan, Seher - Agca, Can Ali. “Kanser Tedavisinde Yeni Bir Yaklaşım ‘Proteoliz Hedefli Kimera’”. Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi 6/2 (Temmuz 2023), 1611-1640.
JAMA Saruhan S, Agca CA. Kanser Tedavisinde Yeni Bir Yaklaşım “Proteoliz Hedefli Kimera”. OKÜ Fen Bil. Ens. Dergisi ((OKU Journal of Nat. & App. Sci). 2023;6:1611–1640.
MLA Saruhan, Seher ve Can Ali Agca. “Kanser Tedavisinde Yeni Bir Yaklaşım ‘Proteoliz Hedefli Kimera’”. Osmaniye Korkut Ata Üniversitesi Fen Bilimleri Enstitüsü Dergisi, c. 6, sy. 2, 2023, ss. 1611-40.
Vancouver Saruhan S, Agca CA. Kanser Tedavisinde Yeni Bir Yaklaşım “Proteoliz Hedefli Kimera”. OKÜ Fen Bil. Ens. Dergisi ((OKU Journal of Nat. & App. Sci). 2023;6(2):1611-40.

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