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result sql = Defects in apoptotic pathways can promote cancer cell survival and also confer resistance to antineoplastic drugs. One pathway being targeted for antineoplastic therapy is the anti-apoptotic B-cell lymphoma-2 (Bcl-2) family of proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that bind to and inactivate BH3-domain pro-apoptotic proteins. Signals transmitted by cellular damage (including antineoplastic drugs) or cytokine deprivation can initiate apoptosis via the intrinsic apoptotic pathway. It is controversial whether some BH3-domain proteins (Bim or tBid) directly activate multidomain pro-apoptotic proteins (e.g., Bax and Bak) or act via inhibition of those anti-apoptotic Bcl-2 proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that stabilize pro-apoptotic proteins. Overexpression of anti-apoptotic Bcl-2 family members has been associated with chemotherapy resistance in various human cancers, and preclinical studies have shown that agents targeting anti-apoptotic Bcl-2 family members have preclinical activity as single agents and in combination with other antineoplastic agents. Clinical trials of several investigational drugs targeting the Bcl-2 family (oblimersen sodium, AT-101, ABT-263, GX15-070) are ongoing. Here, we review the role of the Bcl-2 family in apoptotic pathways and those agents that are known and/or designed to inhibit the anti-apoptotic Bcl-2 family of proteins.
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result sql = Bcl-2 inhibitors: targeting mitochondrial apoptotic pathways in cancer therapy.
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char = i;code = 105
char = l;code = 108
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char = f;code = 102
char = ;code = 32
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char = t;code = 116
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char = i;code = 105
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char = c;code = 99
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char = B;code = 66
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char = X;code = 88
char = L;code = 76
char = ,;code = 44
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char = B;code = 66
char = c;code = 99
char = l;code = 108
char = -;code = 45
char = w;code = 119
char = ,;code = 44
char = ;code = 32
char = M;code = 77
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char = -;code = 45
char = 1;code = 49
char = ,;code = 44
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char = B;code = 66
char = f;code = 102
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char = A;code = 65
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char = a;code = 97
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char = B;code = 66
char = c;code = 99
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char = B;code = 66
char = );code = 41
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = b;code = 98
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char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
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char = a;code = 97
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char = n;code = 110
char = a;code = 97
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char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = B;code = 66
char = H;code = 72
char = 3;code = 51
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char = o;code = 111
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
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char = p;code = 112
char = r;code = 114
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char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
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char = i;code = 105
char = c;code = 99
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char = p;code = 112
char = r;code = 114
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char = t;code = 116
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char = s;code = 115
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char = S;code = 83
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char = g;code = 103
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = s;code = 115
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char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = s;code = 115
char = m;code = 109
char = i;code = 105
char = t;code = 116
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char = e;code = 101
char = d;code = 100
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char = b;code = 98
char = y;code = 121
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char = c;code = 99
char = e;code = 101
char = l;code = 108
char = l;code = 108
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = r;code = 114
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char = d;code = 100
char = a;code = 97
char = m;code = 109
char = a;code = 97
char = g;code = 103
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = i;code = 105
char = n;code = 110
char = c;code = 99
char = l;code = 108
char = u;code = 117
char = d;code = 100
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char = n;code = 110
char = g;code = 103
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = n;code = 110
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char = o;code = 111
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = s;code = 115
char = );code = 41
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = p;code = 112
char = r;code = 114
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = t;code = 116
char = i;code = 105
char = a;code = 97
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char = e;code = 101
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char = a;code = 97
char = p;code = 112
char = o;code = 111
char = p;code = 112
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char = o;code = 111
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char = i;code = 105
char = s;code = 115
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char = v;code = 118
char = i;code = 105
char = a;code = 97
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char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = t;code = 116
char = r;code = 114
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char = n;code = 110
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char = i;code = 105
char = c;code = 99
char = ;code = 32
char = a;code = 97
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char = o;code = 111
char = p;code = 112
char = t;code = 116
char = o;code = 111
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char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = t;code = 116
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char = w;code = 119
char = a;code = 97
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char = .;code = 46
char = ;code = 32
char = I;code = 73
char = t;code = 116
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char = i;code = 105
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = t;code = 116
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char = r;code = 114
char = s;code = 115
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = B;code = 66
char = H;code = 72
char = 3;code = 51
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char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
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char = p;code = 112
char = r;code = 114
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = s;code = 115
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char = (;code = 40
char = B;code = 66
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char = m;code = 109
char = ;code = 32
char = o;code = 111
char = r;code = 114
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char = t;code = 116
char = B;code = 66
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char = d;code = 100
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char = ;code = 32
char = d;code = 100
char = i;code = 105
char = r;code = 114
char = e;code = 101
char = c;code = 99
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char = l;code = 108
char = y;code = 121
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char = a;code = 97
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char = i;code = 105
char = v;code = 118
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = m;code = 109
char = u;code = 117
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char = t;code = 116
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char = m;code = 109
char = a;code = 97
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char = -;code = 45
char = a;code = 97
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char = o;code = 111
char = p;code = 112
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char = ,;code = 44
char = ;code = 32
char = B;code = 66
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char = X;code = 88
char = L;code = 76
char = ,;code = 44
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char = B;code = 66
char = c;code = 99
char = l;code = 108
char = -;code = 45
char = w;code = 119
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char = M;code = 77
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char = 1;code = 49
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char = B;code = 66
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char = 1;code = 49
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char = A;code = 65
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char = 1;code = 49
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = d;code = 100
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char = a;code = 97
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char = i;code = 105
char = z;code = 122
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char = i;code = 105
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char = p;code = 112
char = r;code = 114
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char = e;code = 101
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char = s;code = 115
char = .;code = 46
char = ;code = 32
char = O;code = 79
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char = r;code = 114
char = e;code = 101
char = x;code = 120
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char = e;code = 101
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char = s;code = 115
char = i;code = 105
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char = f;code = 102
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char = a;code = 97
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char = o;code = 111
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char = l;code = 108
char = y;code = 121
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char = m;code = 109
char = b;code = 98
char = e;code = 101
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char = a;code = 97
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char = a;code = 97
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char = s;code = 115
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char = w;code = 119
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char = i;code = 105
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char = a;code = 97
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char = i;code = 105
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char = n;code = 110
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char = s;code = 115
char = .;code = 46
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char = C;code = 67
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char = o;code = 111
char = f;code = 102
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char = s;code = 115
char = e;code = 101
char = v;code = 118
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char = r;code = 114
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result sql = Defects in apoptotic pathways can promote cancer cell survival and also confer resistance to antineoplastic drugs. One pathway being targeted for antineoplastic therapy is the anti-apoptotic B-cell lymphoma-2 (Bcl-2) family of proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that bind to and inactivate BH3-domain pro-apoptotic proteins. Signals transmitted by cellular damage (including antineoplastic drugs) or cytokine deprivation can initiate apoptosis via the intrinsic apoptotic pathway. It is controversial whether some BH3-domain proteins (Bim or tBid) directly activate multidomain pro-apoptotic proteins (e.g., Bax and Bak) or act via inhibition of those anti-apoptotic Bcl-2 proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that stabilize pro-apoptotic proteins. Overexpression of anti-apoptotic Bcl-2 family members has been associated with chemotherapy resistance in various human cancers, and preclinical studies have shown that agents targeting anti-apoptotic Bcl-2 family members have preclinical activity as single agents and in combination with other antineoplastic agents. Clinical trials of several investigational drugs targeting the Bcl-2 family (oblimersen sodium, AT-101, ABT-263, GX15-070) are ongoing. Here, we review the role of the Bcl-2 family in apoptotic pathways and those agents that are known and/or designed to inhibit the anti-apoptotic Bcl-2 family of proteins.
Publication: Clin. Cancer Res. 2009 Feb 15 ;15(4)::1126-32. :doi: 10.1158/1078-0432.CCR-08-0144.
Publication Date: 2009 Feb 15
Study Author(s): Kang, Min H;Reynolds, C Patrick;
Institution: Cancer Center and the Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.
Shortcut link to this study:
Publication Date: 2009 Feb 15
Study Author(s): Kang, Min H;Reynolds, C Patrick;
Institution: Cancer Center and the Department of Cell Biology and Biochemistry, School of Medicine, Texas Tech University Health Sciences Center, Lubbock, Texas 79430, USA.
Shortcut link to this study:
Defects in apoptotic pathways can promote cancer cell survival and also confer resistance to antineoplastic drugs. One pathway being targeted for antineoplastic therapy is the anti-apoptotic B-cell lymphoma-2 (Bcl-2) family of proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that bind to and inactivate BH3-domain pro-apoptotic proteins. Signals transmitted by cellular damage (including antineoplastic drugs) or cytokine deprivation can initiate apoptosis via the intrinsic apoptotic pathway. It is controversial whether some BH3-domain proteins (Bim or tBid) directly activate multidomain pro-apoptotic proteins (e.g., Bax and Bak) or act via inhibition of those anti-apoptotic Bcl-2 proteins (Bcl-2, Bcl-XL, Bcl-w, Mcl-1, Bfl1/A-1, and Bcl-B) that stabilize pro-apoptotic proteins. Overexpression of anti-apoptotic Bcl-2 family members has been associated with chemotherapy resistance in various human cancers, and preclinical studies have shown that agents targeting anti-apoptotic Bcl-2 family members have preclinical activity as single agents and in combination with other antineoplastic agents. Clinical trials of several investigational drugs targeting the Bcl-2 family (oblimersen sodium, AT-101, ABT-263, GX15-070) are ongoing. Here, we review the role of the Bcl-2 family in apoptotic pathways and those agents that are known and/or designed to inhibit the anti-apoptotic Bcl-2 family of proteins.
PMID: 19228717
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