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Discovery and optimization of covalent Bcl-xL antagonists
Bioorganic & Medicinal Chemistry Letters, 2019Over the last ten years, targeted covalent inhibition has become a key discipline within medicinal chemistry research, most notably in the development of oncology therapeutics. One area where this approach is underrepresented, however, is in targeting protein-protein interactions.
Herschel, Mukherjee +7 more
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Bcl-xL overexpression restricts γ-radiation-induced apoptosis
Cell Biology International, 2006Bcl-xL belongs to a family of proteins which inhibit apoptosis in a number of stimuli including ionizing radiation. To better understand the effects and mechanisms of Bcl-xL on the apoptosis of lymphocytes and provide experimental basis to treat immune injury induced by radiation, we used normal human lymphoblastoid AHH-1 cells that were engineered to ...
Zi-Bing, Wang +6 more
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Bcl-xL as an antiapoptotic molecule for cardiomyocytes
Drug News & Perspectives, 2003It is now widely accepted that two forms of cell death, apoptosis and necrosis, occur in cardiomyocytes, and increasing evidence indicates that apoptosis plays an important role in the pathophysiology of cardiovascular diseases. Currently, two major pathways in the induction of apoptosis are known to occur in cardiomyocytes, the mitochondrial pathway ...
Yukiyo, Ogata, Masafumi, Takahashi
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Bcl-xL Antisense Oligonucleotides Chemosensitize Human Glioblastoma Cells
Chemotherapy, 2002<i>Background:</i> Resistance to chemotherapy in glioblastoma has been linked to the expression of antiapoptotic Bcl-2 family members including Bcl-xL. <i>Methods:</i> Bcl-xL expression was specifically reduced in M059K glioblastoma cells with antisense oligonucleotides (ISIS 16009, ISIS 16967) as assessed by Western blotting ...
Patrick, Guensberg +6 more
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Bax-independent inhibition of apoptosis by Bcl-XL
Nature, 1996The Bcl-2-related protein, Bcl-XL, has been shown to block apoptosis induced by a variety of stimuli and to be a stronger protector against apoptosis than Bcl-2 under certain circumstances. Using site-specific mutagenesis, we show here that the amino-acid residues critical for protection of cells by Bcl-XL against Sindbis virus-induced apoptosis are ...
E H, Cheng +4 more
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BCL-XL Dimerization by Three-dimensional Domain Swapping
Journal of Molecular Biology, 2006Dimeric interactions among anti- and pro-apoptotic members of the BCL-2 protein family are dynamically regulated and intimately involved in survival and death functions. We report the structure of a BCL-X(L) homodimers a 3D-domain swapped dimer (3DDS).
Jason W, O'Neill +3 more
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Discovery of Xz338, a Highly Potent Bcl-Xl Degrader
European Journal of Medicinal ChemistryBCL-XL is a crucial anti-apoptotic protein involved in tumorigenesis and resistance to cancer chemotherapy. Transitioning from conventional inhibitors to PROTAC degraders has shown promising potential, particularly in minimizing the on-target thrombocytopenia linked to BCL-XL inhibition.
Xuan Zhang +7 more
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Bcl-xL Deamidation a Trigger for Apoptosis
Science's STKE, 2007Using a transgenic mouse as a model for T cell lymphoma, Zhao et al . provide evidence that defective deamidation of Bcl-xL contributes to the apoptosis resistance and oncogenesis of thymocytes in these animals. These mice ( CD45 −/− lck F505
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