Selective targeting of antiapoptotic BCL-2 proteins in cancer

Timuçin, Ahmet Can and Başağa, Hüveyda and Kütük, Özgür (2019) Selective targeting of antiapoptotic BCL-2 proteins in cancer. Medicinal Research Reviews, 39 (1). pp. 146-175. ISSN 0198-6325 (Print) 1098-1128 (Online)

This is the latest version of this item.

Full text not available from this repository. (Request a copy)


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 BCL2/ 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.
Item Type: Article
Uncontrolled Keywords: antiapoptotic BCL-2 proteins; cancer; small molecules; targeted therapy
Divisions: Faculty of Engineering and Natural Sciences > Academic programs > Biological Sciences & Bio Eng.
Faculty of Engineering and Natural Sciences
Depositing User: Hüveyda Başağa
Date Deposited: 22 May 2019 11:57
Last Modified: 27 May 2023 21:01

Available Versions of this Item

Actions (login required)

View Item
View Item