|
|
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result sql = Vitamin D analogues targeting CYP24 in chronic kidney disease.
Vitamin D analogues targeting CYP24 in chronic kidney disease.char = T;code = 84
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char = t;code = 116
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char = t;code = 116
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char = o;code = 111
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char = ;code = 32
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char = h;code = 104
char = e;code = 101
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char = b;code = 98
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char = l;code = 108
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char = ;code = 32
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char = a;code = 97
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char = e;code = 101
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char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = ;code = 32
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result sql = The cytochrome P450 enzyme 24-hydroxylase (CYP24) plays a critical role in regulating levels of vitamin D hormone. Aberrant expression of CYP24 has been implicated in vitamin D insufficiency and resistance to vitamin D therapy. We have demonstrated amplified CYP24 expression in uremic rats, suggesting that CYP24 has an etiological role in vitamin D insufficiency commonly associated with chronic kidney disease (CKD). We have designed two new analogues of 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3), namely CTA091 and CTA018/MT2832, which are potent inhibitors of CYP24. In vitro studies with CTA091 show that it enhances the potency of 1alpha,25(OH)2D3. In vivo studies demonstrate that CTA091 decreases serum intact parathyroid hormone (iPTH) levels and increases circulating 1alpha,25(OH)2D3. CTA091 increases both Cmax and AUC of co-administered 1alpha,25(OH)2D3. These studies indicate that CYP24 inhibition can increase cellular responsiveness to vitamin D hormone and potentiate vitamin D therapy. CTA018/MT2832 differs from CTA091 in that it also has the ability to activate vitamin D receptor-mediated transcription. CTA018/MT2832 effectively suppresses elevated iPTH secretion at doses which do not affect serum calcium or phosphorus levels in a rodent model of CKD. Studies with both new analogues underscore the potential utility of CYP24 inhibition in the treatment of secondary hyperparathyroidism in CKD.
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char = o;code = 111
char = g;code = 103
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char = t;code = 116
char = a;code = 97
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char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
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char = C;code = 67
char = Y;code = 89
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char = 2;code = 50
char = 4;code = 52
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char = i;code = 105
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char = h;code = 104
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char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = .;code = 46
result sql = Vitamin D analogues targeting CYP24 in chronic kidney disease.
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char = l;code = 108
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char = e;code = 101
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char = r;code = 114
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char = .;code = 46
char = ;code = 32
char = W;code = 87
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char = h;code = 104
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char = m;code = 109
char = p;code = 112
char = l;code = 108
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char = f;code = 102
char = i;code = 105
char = e;code = 101
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char = ;code = 32
char = C;code = 67
char = Y;code = 89
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char = 2;code = 50
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char = ;code = 32
char = e;code = 101
char = x;code = 120
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char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
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char = o;code = 111
char = n;code = 110
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = u;code = 117
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
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char = a;code = 97
char = t;code = 116
char = s;code = 115
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char = ;code = 32
char = s;code = 115
char = u;code = 117
char = g;code = 103
char = g;code = 103
char = e;code = 101
char = s;code = 115
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char = i;code = 105
char = n;code = 110
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = C;code = 67
char = Y;code = 89
char = P;code = 80
char = 2;code = 50
char = 4;code = 52
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = ;code = 32
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = o;code = 111
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char = o;code = 111
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char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = o;code = 111
char = l;code = 108
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = D;code = 68
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = s;code = 115
char = u;code = 117
char = f;code = 102
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = i;code = 105
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
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char = c;code = 99
char = o;code = 111
char = m;code = 109
char = m;code = 109
char = o;code = 111
char = n;code = 110
char = l;code = 108
char = y;code = 121
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char = a;code = 97
char = s;code = 115
char = s;code = 115
char = o;code = 111
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char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = o;code = 111
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char = i;code = 105
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char = k;code = 107
char = i;code = 105
char = d;code = 100
char = n;code = 110
char = e;code = 101
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char = d;code = 100
char = i;code = 105
char = s;code = 115
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = (;code = 40
char = C;code = 67
char = K;code = 75
char = D;code = 68
char = );code = 41
char = .;code = 46
char = ;code = 32
char = W;code = 87
char = e;code = 101
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = g;code = 103
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char = e;code = 101
char = d;code = 100
char = ;code = 32
char = t;code = 116
char = w;code = 119
char = o;code = 111
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = w;code = 119
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = u;code = 117
char = e;code = 101
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = 1;code = 49
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
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char = d;code = 100
char = i;code = 105
char = h;code = 104
char = y;code = 121
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = x;code = 120
char = y;code = 121
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char = i;code = 105
char = t;code = 116
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = D;code = 68
char = 3;code = 51
char = ;code = 32
char = (;code = 40
char = 1;code = 49
char = a;code = 97
char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = n;code = 110
char = a;code = 97
char = m;code = 109
char = e;code = 101
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = C;code = 67
char = T;code = 84
char = A;code = 65
char = 0;code = 48
char = 9;code = 57
char = 1;code = 49
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = C;code = 67
char = T;code = 84
char = A;code = 65
char = 0;code = 48
char = 1;code = 49
char = 8;code = 56
char = /;code = 47
char = M;code = 77
char = T;code = 84
char = 2;code = 50
char = 8;code = 56
char = 3;code = 51
char = 2;code = 50
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = h;code = 104
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = s;code = 115
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = C;code = 67
char = Y;code = 89
char = P;code = 80
char = 2;code = 50
char = 4;code = 52
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = r;code = 114
char = o;code = 111
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char = s;code = 115
char = t;code = 116
char = u;code = 117
char = d;code = 100
char = i;code = 105
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = C;code = 67
char = T;code = 84
char = A;code = 65
char = 0;code = 48
char = 9;code = 57
char = 1;code = 49
char = ;code = 32
char = s;code = 115
char = h;code = 104
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
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char = i;code = 105
char = t;code = 116
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char = e;code = 101
char = n;code = 110
char = h;code = 104
char = a;code = 97
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char = c;code = 99
char = e;code = 101
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char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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char = p;code = 112
char = o;code = 111
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = c;code = 99
char = y;code = 121
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char = o;code = 111
char = f;code = 102
char = ;code = 32
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char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
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char = 2;code = 50
char = 5;code = 53
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
char = ;code = 32
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = o;code = 111
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char = s;code = 115
char = t;code = 116
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char = i;code = 105
char = e;code = 101
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char = d;code = 100
char = e;code = 101
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char = s;code = 115
char = t;code = 116
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char = a;code = 97
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char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = ;code = 32
char = C;code = 67
char = T;code = 84
char = A;code = 65
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char = 9;code = 57
char = 1;code = 49
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char = a;code = 97
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char = s;code = 115
char = ;code = 32
char = s;code = 115
char = e;code = 101
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char = m;code = 109
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char = i;code = 105
char = n;code = 110
char = t;code = 116
char = a;code = 97
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char = p;code = 112
char = a;code = 97
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char = a;code = 97
char = t;code = 116
char = h;code = 104
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char = r;code = 114
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char = d;code = 100
char = ;code = 32
char = h;code = 104
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = o;code = 111
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char = e;code = 101
char = ;code = 32
char = (;code = 40
char = i;code = 105
char = P;code = 80
char = T;code = 84
char = H;code = 72
char = );code = 41
char = ;code = 32
char = l;code = 108
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = l;code = 108
char = s;code = 115
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char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = c;code = 99
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char = r;code = 114
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = 1;code = 49
char = a;code = 97
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char = p;code = 112
char = h;code = 104
char = a;code = 97
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = T;code = 84
char = A;code = 65
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char = 9;code = 57
char = 1;code = 49
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char = i;code = 105
char = n;code = 110
char = c;code = 99
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = b;code = 98
char = o;code = 111
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = C;code = 67
char = m;code = 109
char = a;code = 97
char = x;code = 120
char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = A;code = 65
char = U;code = 85
char = C;code = 67
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = c;code = 99
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char = -;code = 45
char = a;code = 97
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char = m;code = 109
char = i;code = 105
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char = i;code = 105
char = s;code = 115
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char = e;code = 101
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char = e;code = 101
char = d;code = 100
char = ;code = 32
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char = l;code = 108
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = ,;code = 44
char = 2;code = 50
char = 5;code = 53
char = (;code = 40
char = O;code = 79
char = H;code = 72
char = );code = 41
char = 2;code = 50
char = D;code = 68
char = 3;code = 51
char = .;code = 46
char = ;code = 32
char = T;code = 84
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
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char = s;code = 115
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char = u;code = 117
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char = i;code = 105
char = c;code = 99
char = a;code = 97
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char = e;code = 101
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char = t;code = 116
char = h;code = 104
char = a;code = 97
char = t;code = 116
char = ;code = 32
char = C;code = 67
char = Y;code = 89
char = P;code = 80
char = 2;code = 50
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char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = i;code = 105
char = b;code = 98
char = i;code = 105
char = t;code = 116
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char = o;code = 111
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char = ;code = 32
char = c;code = 99
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char = i;code = 105
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char = e;code = 101
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char = a;code = 97
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char = t;code = 116
char = o;code = 111
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char = v;code = 118
char = i;code = 105
char = t;code = 116
char = a;code = 97
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char = i;code = 105
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char = a;code = 97
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char = e;code = 101
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char = v;code = 118
char = i;code = 105
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char = a;code = 97
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char = i;code = 105
char = n;code = 110
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char = D;code = 68
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = y;code = 121
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char = ;code = 32
char = C;code = 67
char = T;code = 84
char = A;code = 65
char = 0;code = 48
char = 1;code = 49
char = 8;code = 56
char = /;code = 47
char = M;code = 77
char = T;code = 84
char = 2;code = 50
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char = 3;code = 51
char = 2;code = 50
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char = d;code = 100
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char = f;code = 102
char = f;code = 102
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char = r;code = 114
char = s;code = 115
char = ;code = 32
char = f;code = 102
char = r;code = 114
char = o;code = 111
char = m;code = 109
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char = C;code = 67
char = T;code = 84
char = A;code = 65
char = 0;code = 48
char = 9;code = 57
char = 1;code = 49
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char = i;code = 105
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = s;code = 115
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char = a;code = 97
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char = t;code = 116
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char = t;code = 116
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char = a;code = 97
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char = v;code = 118
char = a;code = 97
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char = e;code = 101
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char = t;code = 116
char = a;code = 97
char = m;code = 109
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char = n;code = 110
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char = D;code = 68
char = ;code = 32
char = r;code = 114
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char = c;code = 99
char = e;code = 101
char = p;code = 112
char = t;code = 116
char = o;code = 111
char = r;code = 114
char = -;code = 45
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char = e;code = 101
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char = a;code = 97
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char = e;code = 101
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char = a;code = 97
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char = s;code = 115
char = c;code = 99
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char = i;code = 105
char = p;code = 112
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = .;code = 46
char = ;code = 32
char = C;code = 67
char = T;code = 84
char = A;code = 65
char = 0;code = 48
char = 1;code = 49
char = 8;code = 56
char = /;code = 47
char = M;code = 77
char = T;code = 84
char = 2;code = 50
char = 8;code = 56
char = 3;code = 51
char = 2;code = 50
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
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char = t;code = 116
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char = v;code = 118
char = e;code = 101
char = l;code = 108
char = y;code = 121
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char = s;code = 115
char = u;code = 117
char = p;code = 112
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = s;code = 115
char = e;code = 101
char = s;code = 115
char = ;code = 32
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result sql = The cytochrome P450 enzyme 24-hydroxylase (CYP24) plays a critical role in regulating levels of vitamin D hormone. Aberrant expression of CYP24 has been implicated in vitamin D insufficiency and resistance to vitamin D therapy. We have demonstrated amplified CYP24 expression in uremic rats, suggesting that CYP24 has an etiological role in vitamin D insufficiency commonly associated with chronic kidney disease (CKD). We have designed two new analogues of 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3), namely CTA091 and CTA018/MT2832, which are potent inhibitors of CYP24. In vitro studies with CTA091 show that it enhances the potency of 1alpha,25(OH)2D3. In vivo studies demonstrate that CTA091 decreases serum intact parathyroid hormone (iPTH) levels and increases circulating 1alpha,25(OH)2D3. CTA091 increases both Cmax and AUC of co-administered 1alpha,25(OH)2D3. These studies indicate that CYP24 inhibition can increase cellular responsiveness to vitamin D hormone and potentiate vitamin D therapy. CTA018/MT2832 differs from CTA091 in that it also has the ability to activate vitamin D receptor-mediated transcription. CTA018/MT2832 effectively suppresses elevated iPTH secretion at doses which do not affect serum calcium or phosphorus levels in a rodent model of CKD. Studies with both new analogues underscore the potential utility of CYP24 inhibition in the treatment of secondary hyperparathyroidism in CKD.
Publication: J. Steroid Biochem. Mol. Biol. 2010 Jul ;121(1-2)::13-9. :doi: 10.1016/j.jsbmb.2010.03.065.
Publication Date: 2010 Jul
Study Author(s): Posner, Gary H;Helvig, Christian;Cuerrier, Dominic;Collop, Drew;Kharebov, Aza;Ryder, Kara;Epps, Tina;Petkovich, Martin;
Institution: Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA.
Shortcut link to this study:
Publication Date: 2010 Jul
Study Author(s): Posner, Gary H;Helvig, Christian;Cuerrier, Dominic;Collop, Drew;Kharebov, Aza;Ryder, Kara;Epps, Tina;Petkovich, Martin;
Institution: Department of Chemistry, The Johns Hopkins University, Baltimore, MD 21218, USA.
Shortcut link to this study:
The cytochrome P450 enzyme 24-hydroxylase (CYP24) plays a critical role in regulating levels of vitamin D hormone. Aberrant expression of CYP24 has been implicated in vitamin D insufficiency and resistance to vitamin D therapy. We have demonstrated amplified CYP24 expression in uremic rats, suggesting that CYP24 has an etiological role in vitamin D insufficiency commonly associated with chronic kidney disease (CKD). We have designed two new analogues of 1alpha,25-dihydroxyvitamin D3 (1alpha,25(OH)2D3), namely CTA091 and CTA018/MT2832, which are potent inhibitors of CYP24. In vitro studies with CTA091 show that it enhances the potency of 1alpha,25(OH)2D3. In vivo studies demonstrate that CTA091 decreases serum intact parathyroid hormone (iPTH) levels and increases circulating 1alpha,25(OH)2D3. CTA091 increases both Cmax and AUC of co-administered 1alpha,25(OH)2D3. These studies indicate that CYP24 inhibition can increase cellular responsiveness to vitamin D hormone and potentiate vitamin D therapy. CTA018/MT2832 differs from CTA091 in that it also has the ability to activate vitamin D receptor-mediated transcription. CTA018/MT2832 effectively suppresses elevated iPTH secretion at doses which do not affect serum calcium or phosphorus levels in a rodent model of CKD. Studies with both new analogues underscore the potential utility of CYP24 inhibition in the treatment of secondary hyperparathyroidism in CKD.
PMID: 20347976
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