Portal de Periódicos da CAPES

Selective targeting of antiapoptotic BCL‐2 proteins in cancer

2018; Wiley; Volume: 39; Issue: 1 Linguagem: Inglês

10.1002/med.21516

1098-1128

Ahmet Can Timuçin, Hüveyda Başağa, Özgür Kütük,

Nanoparticle-Based Drug Delivery

Medicinal Research ReviewsVolume 39, Issue 1 p. 146-175 REVIEW ARTICLE Selective targeting of antiapoptotic BCL-2 proteins in cancer Ahmet Can Timucin, Corresponding Author Ahmet Can Timucin ahmetcan.timucin@uskudar.edu.tr cantimucin@sabanciuniv.edu orcid.org/0000-0002-9483-3593 Faculty of Engineering and Natural Sciences, Department of Chemical and Biological Engineering, Uskudar University, Uskudar, Istanbul, Turkey Faculty of Engineering and Natural Sciences, Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Tuzla, Istanbul, Turkey Correspondence Ahmet Can Timucin, Faculty of Engineering and Natural Sciences, Department of Chemical and Biological Engineering, Uskudar University, Altunizade Mahallesi, Haluk Turksoy Sk. No:14, 34662 Uskudar, Istanbul, Turkey. Email: ahmetcan.timucin@uskudar.edu.tr/ cantimucin@sabanciuniv.eduSearch for more papers by this authorHuveyda Basaga, Huveyda Basaga Faculty of Engineering and Natural Sciences, Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Tuzla, Istanbul, TurkeySearch for more papers by this authorOzgur Kutuk, Ozgur Kutuk Department of Medical Genetics, Adana Medical and Research Center, School of Medicine, Baskent University, Yuregir, Adana, TurkeySearch for more papers by this author Ahmet Can Timucin, Corresponding Author Ahmet Can Timucin ahmetcan.timucin@uskudar.edu.tr cantimucin@sabanciuniv.edu orcid.org/0000-0002-9483-3593 Faculty of Engineering and Natural Sciences, Department of Chemical and Biological Engineering, Uskudar University, Uskudar, Istanbul, Turkey Faculty of Engineering and Natural Sciences, Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Tuzla, Istanbul, Turkey Correspondence Ahmet Can Timucin, Faculty of Engineering and Natural Sciences, Department of Chemical and Biological Engineering, Uskudar University, Altunizade Mahallesi, Haluk Turksoy Sk. No:14, 34662 Uskudar, Istanbul, Turkey. Email: ahmetcan.timucin@uskudar.edu.tr/ cantimucin@sabanciuniv.eduSearch for more papers by this authorHuveyda Basaga, Huveyda Basaga Faculty of Engineering and Natural Sciences, Molecular Biology, Genetics and Bioengineering Program, Sabanci University, Tuzla, Istanbul, TurkeySearch for more papers by this authorOzgur Kutuk, Ozgur Kutuk Department of Medical Genetics, Adana Medical and Research Center, School of Medicine, Baskent University, Yuregir, Adana, TurkeySearch for more papers by this author First published: 30 May 2018 https://doi.org/10.1002/med.21516Citations: 41Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract Circumvention of apoptotic machinery is one of the distinctive properties of carcinogenesis. Extensively established key effectors of such apoptotic bypass mechanisms, the antiapoptotic BCL-2 (apoptosis regulator BCL-2) proteins, determine the response of cancer cells to chemotherapeutics. Within this background, research and development of antiapoptotic BCL-2 inhibitors were considered to have a tremendous amount of potential toward the discovery of novel pharmacological modulators in cancer. In this review, milestone achievements in the development of selective antiapoptotic BCL-2 proteins inhibitors for BCL-2, BCL-XL (BCL-2-like protein 1), and MCL-1 (induced myeloid leukemia cell differentiation protein MCL-1) were summarized and their future implications were discussed. In the first section, the design and development of BCL-2/BCL-XL dual inhibitor navitoclax, as well as the recent advances and clinical experience with selective BCL-2 inhibitor venetoclax, were synopsized. Preclinical data from selective BCL-XL inhibitors, which are currently undergoing extensive testing as a single agent or in combination with other therapeutic agents, were further summarized. In the second section, MCL-1 inhibitors developed as potential anticancer agents were reviewed regarding their specificity toward MCL-1. Explicitly, studies leading to the identification of MCL-1, nonselective and selective targeting of MCL-1, and recently initiated clinical trials were compiled in chronological order. Based on these concepts, future directions were further discussed for increasing selectivity in the design of prosurvival BCL-2 member inhibitors. Citing Literature Volume39, Issue1January 2019Pages 146-175 RelatedInformation