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Designing selective small molecule inhibitor screening through BH3 profiling

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Karataş, Sevde Nur (2018) Designing selective small molecule inhibitor screening through BH3 profiling. [Thesis]

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Official URL: http://risc01.sabanciuniv.edu/record=b1817036 (Table of Contents)

Abstract

Apoptotic cell death is a crucial programmed mechanism for homeostasis of tissue. Mitochondrial apoptotic cell death is governed by BCL-2 protein family members. Aberrations in mitochondrial-mediated apoptosis lead to impaired cell death signaling in response to cellular damage and thereby promotes cancer cell survival. Upon with selectively interacting antiapoptotic BCL-2 proteins, BH3-only BCL-2 proteins play a crucial role in governing cellular damage. All anti-apoptotic members of the BCL-2 protein family share a BH3 death domain, thus BH3 profiling enables us to assess the apoptotic blocks caused by cancer cells. The myeloid cell leukemia-1 protein encoded by MCL-1 gene and is an anti-apoptotic member of a BCL-2 protein family. It is known as a survival molecule for the cancer cells and overexpression of it confers a resistance against chemotherapeutic drugs for the treatment of several types of cancer. These findings point out that the significance of the small molecule inhibitor for MCL-1. We have designed a small molecule inhibitor screening with the aid of the automated pipetting system, epMotion5070, through BH3 profiling method to monitor priming to cell death in the context of MCL-1 dependence. We optimized the epMotion5070 by using a library, consisting of kinase inhibitors (80 molecules) for designing small molecule inhibitor screening. Then, we aimed to trigger mitochondrial apoptotic cell death via MCL-1 inhibitor molecules on non-small lung cancer cell lines ( H-23, H-1975) by screening a library (1280 molecules), which is accomplished by BH3 profiling. In this study, we identified specific small molecules for the inhibition of MCL-1.

Item Type:Thesis
Uncontrolled Keywords:MCL-1. -- Apoptosis. -- Mitochondria. -- BH3 Profiling. -- Library screening. -- Miyeloid lösemi. -- Apoptoz. -- Mitokondri. -- BH3 profillemesi. -- BCL-2 protein ailesi.
Subjects:T Technology > TA Engineering (General). Civil engineering (General) > TA164 Bioengineering
ID Code:36580
Deposited By:IC-Cataloging
Deposited On:01 Oct 2018 10:02
Last Modified:22 May 2019 14:11

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