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Details on Person Apoptosis is governed by two pathways that ultimately lead t...
| Class:Id | Summation:9692397 |
|---|---|
| _displayName | Apoptosis is governed by two pathways that ultimately lead t... |
| _timestamp | 2020-06-22 14:14:28 |
| created | [InstanceEdit:9692328] Jassal, Bijay, 2020-06-22 |
| literatureReference | [LiteratureReference:9692394] Targeting the Bcl-2 Family in B Cell Lymphoma [LiteratureReference:9692404] The Role of Inhibition of Apoptosis in Acute Leukemias and Myelodysplastic Syndrome [LiteratureReference:9692326] BH3-Mimetic Drugs: Blazing the Trail for New Cancer Medicines |
| text | Apoptosis is governed by two pathways that ultimately lead to cell death. The extrinsic pathway is activated in response to external signalling proteins and is tightly regulated by the Bcl-2 superfamily of proteins. For a cell in its resting state, BCL family members, acting as suppressors, bind to effectors and activators of apoptosis to suppress their activity. One of the hallmarks of cancer is to evade apoptosis. Changes in the anti-apoptotic protein BCL2 is a hallmark of B-cell lymphoma. BCL2 antagonists are used for B-cell lymphomas and acute leukemias (McBride et al. 2019, Adams et al. 2019, Merino et al. 2018). The first synthetic BH-3 mimetic was ABT-737, a small-molecule that binds with high affinity to BCL-2 family members and was shown to induce apoptosis in some lymphoma cell lines (Paoluzzi et al. 2008, Volger et al. 2008). However, ABT-737 shows poor bioavailability. Navitoclax (ABT-263) is a BH3 mimetic which antagonises the action of Bcl-2 family proteins. It is a re-engineered drug from ABT-737 and shows much higher bioavailability than ABT-737 (Bruncko et al. 2007). Navitoclax induces complete tumour regression in xenograft models of small-cell lung cancer and acute lymphoblastic leukemia (Tse et al. 2008). Venetoclax (ABT-199) is a BH3 mimetic that selectively targets BCL2 and is the only BCL2 antagonist approved for patients with chronic lymphocytic leukemia (CLL) and acute myeloid leukemia (AML) (Souers et al. 2013). Unlike its predecessors, venetoclax is highly selective for BCL2 (Pan et al. 2014). |
| (summation) | [Reaction:9692376] BCL2 binds BCL2 antagonists [Homo sapiens] |
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