|
|
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result sql = Vanadium treatment of type 2 diabetes: a view to the future.
Vanadium treatment of type 2 diabetes: a view to the future.char = 3;code = 51
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result sql = 3-Hydroxy-2-methyl-4-pyrone and 2-ethyl-3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven especially suitable as ligands for vanadyl ions, in potential insulin enhancing agents for diabetes mellitus. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate stability for pro-drug use, and have undergone extensive pre-clinical testing for safety and efficacy. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in bone. These bis-ligand oxovanadium(IV) (VOL(2)) compounds have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability and pharmaceutical efficacy BEOV : has now completed Phase I and has advanced to Phase II clinical trials. In the Phase I trial, a range of doses from 10 mg to 90 mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects; all biochemical parameters remained within normal limits. In the Phase IIa trial, BEOV (AKP-020), 20 mg, daily for 28 days, per os, in seven type 2 diabetic subjects, was associated with reductions in fasting blood glucose and %HbA1c; improved responses to oral glucose tolerance testing, versus the observed worsening of diabetic symptoms in the two placebo controls.
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result sql = Vanadium treatment of type 2 diabetes: a view to the future.
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char = ;code = 32
char = b;code = 98
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char = s;code = 115
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char = a;code = 97
char = l;code = 108
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = o;code = 111
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char = o;code = 111
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char = o;code = 111
char = v;code = 118
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = (;code = 40
char = I;code = 73
char = V;code = 86
char = );code = 41
char = ;code = 32
char = (;code = 40
char = B;code = 66
char = M;code = 77
char = O;code = 79
char = V;code = 86
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = t;code = 116
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char = e;code = 101
char = ;code = 32
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = t;code = 116
char = o;code = 111
char = l;code = 108
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 = ,;code = 44
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = s;code = 115
char = (;code = 40
char = e;code = 101
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = l;code = 108
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = t;code = 116
char = o;code = 111
char = l;code = 108
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = );code = 41
char = o;code = 111
char = x;code = 120
char = o;code = 111
char = v;code = 118
char = a;code = 97
char = n;code = 110
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = (;code = 40
char = I;code = 73
char = V;code = 86
char = );code = 41
char = ;code = 32
char = (;code = 40
char = B;code = 66
char = E;code = 69
char = O;code = 79
char = V;code = 86
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
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char = t;code = 116
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char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = s;code = 115
char = i;code = 105
char = r;code = 114
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char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = ;code = 32
char = s;code = 115
char = t;code = 116
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = -;code = 45
char = d;code = 100
char = r;code = 114
char = u;code = 117
char = g;code = 103
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = e;code = 101
char = r;code = 114
char = g;code = 103
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = -;code = 45
char = c;code = 99
char = l;code = 108
char = i;code = 105
char = n;code = 110
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = t;code = 116
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = a;code = 97
char = f;code = 102
char = e;code = 101
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = c;code = 99
char = y;code = 121
char = .;code = 46
char = ;code = 32
char = P;code = 80
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = o;code = 111
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = e;code = 101
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = u;code = 117
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = i;code = 105
char = r;code = 114
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = p;code = 112
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = d;code = 100
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = o;code = 111
char = c;code = 99
char = i;code = 105
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = n;code = 110
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = s;code = 115
char = e;code = 101
char = r;code = 114
char = u;code = 117
char = m;code = 109
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = s;code = 115
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = c;code = 99
char = i;code = 105
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 = o;code = 111
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char = ;code = 32
char = a;code = 97
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char = d;code = 100
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = a;code = 97
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char = s;code = 115
char = p;code = 112
char = o;code = 111
char = r;code = 114
char = t;code = 116
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char = t;code = 116
char = o;code = 111
char = ;code = 32
char = t;code = 116
char = i;code = 105
char = s;code = 115
char = s;code = 115
char = u;code = 117
char = e;code = 101
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = w;code = 119
char = i;code = 105
char = t;code = 116
char = h;code = 104
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = f;code = 102
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = u;code = 117
char = p;code = 112
char = t;code = 116
char = a;code = 97
char = k;code = 107
char = e;code = 101
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = b;code = 98
char = o;code = 111
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char = e;code = 101
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
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = s;code = 115
char = -;code = 45
char = l;code = 108
char = i;code = 105
char = g;code = 103
char = a;code = 97
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char = d;code = 100
char = ;code = 32
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char = x;code = 120
char = o;code = 111
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char = a;code = 97
char = n;code = 110
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = u;code = 117
char = m;code = 109
char = (;code = 40
char = I;code = 73
char = V;code = 86
char = );code = 41
char = ;code = 32
char = (;code = 40
char = V;code = 86
char = O;code = 79
char = L;code = 76
char = (;code = 40
char = 2;code = 50
char = );code = 41
char = );code = 41
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = o;code = 111
char = u;code = 117
char = n;code = 110
char = d;code = 100
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
char = ;code = 32
char = a;code = 97
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char = c;code = 99
char = l;code = 108
char = e;code = 101
char = a;code = 97
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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 = t;code = 116
char = a;code = 97
char = g;code = 103
char = e;code = 101
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char = o;code = 111
char = v;code = 118
char = e;code = 101
char = r;code = 114
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char = i;code = 105
char = n;code = 110
char = o;code = 111
char = r;code = 114
char = g;code = 103
char = a;code = 97
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char = i;code = 105
char = c;code = 99
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char = v;code = 118
char = a;code = 97
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char = a;code = 97
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char = y;code = 121
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = f;code = 102
char = a;code = 97
char = t;code = 116
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = m;code = 109
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = a;code = 97
char = v;code = 118
char = a;code = 97
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char = l;code = 108
char = a;code = 97
char = b;code = 98
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = c;code = 99
char = e;code = 101
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = c;code = 99
char = y;code = 121
char = <;code = 60
char = b;code = 98
char = >;code = 62
char = ;code = 32
char = B;code = 66
char = E;code = 69
char = O;code = 79
char = V;code = 86
char = ;code = 32
char = :;code = 58
char = ;code = 32
char = <;code = 60
char = /;code = 47
char = b;code = 98
char = >;code = 62
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = w;code = 119
char = ;code = 32
char = c;code = 99
char = o;code = 111
char = m;code = 109
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = P;code = 80
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = I;code = 73
char = ;code = 32
char = a;code = 97
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char = a;code = 97
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char = P;code = 80
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = e;code = 101
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char = I;code = 73
char = I;code = 73
char = ;code = 32
char = c;code = 99
char = l;code = 108
char = i;code = 105
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char = c;code = 99
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char = t;code = 116
char = r;code = 114
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char = a;code = 97
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char = s;code = 115
char = .;code = 46
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char = I;code = 73
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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 = 80
char = h;code = 104
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = I;code = 73
char = ;code = 32
char = t;code = 116
char = r;code = 114
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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char = r;code = 114
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
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char = o;code = 111
char = f;code = 102
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = s;code = 115
char = e;code = 101
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 = 1;code = 49
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = 9;code = 57
char = 0;code = 48
char = ;code = 32
char = m;code = 109
char = g;code = 103
char = ;code = 32
char = B;code = 66
char = E;code = 69
char = O;code = 79
char = V;code = 86
char = ,;code = 44
char = ;code = 32
char = g;code = 103
char = i;code = 105
char = v;code = 118
char = e;code = 101
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = ;code = 32
char = n;code = 110
char = o;code = 111
char = n;code = 110
char = -;code = 45
char = d;code = 100
char = i;code = 105
char = a;code = 97
char = b;code = 98
char = e;code = 101
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = v;code = 118
char = o;code = 111
char = l;code = 108
char = u;code = 117
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ,;code = 44
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = n;code = 110
char = o;code = 111
char = ;code = 32
char = a;code = 97
char = d;code = 100
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = f;code = 102
char = f;code = 102
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = s;code = 115
char = ;;code = 59
char = ;code = 32
char = a;code = 97
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char = l;code = 108
char = ;code = 32
char = b;code = 98
char = i;code = 105
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = m;code = 109
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = s;code = 115
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
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 = i;code = 105
char = n;code = 110
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char = n;code = 110
char = o;code = 111
char = r;code = 114
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = l;code = 108
char = i;code = 105
char = m;code = 109
char = i;code = 105
char = t;code = 116
char = s;code = 115
char = .;code = 46
char = ;code = 32
char = I;code = 73
char = n;code = 110
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char = ,;code = 44
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
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char = i;code = 105
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result sql = 3-Hydroxy-2-methyl-4-pyrone and 2-ethyl-3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven especially suitable as ligands for vanadyl ions, in potential insulin enhancing agents for diabetes mellitus. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate stability for pro-drug use, and have undergone extensive pre-clinical testing for safety and efficacy. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in bone. These bis-ligand oxovanadium(IV) (VOL(2)) compounds have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability and pharmaceutical efficacy BEOV : has now completed Phase I and has advanced to Phase II clinical trials. In the Phase I trial, a range of doses from 10 mg to 90 mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects; all biochemical parameters remained within normal limits. In the Phase IIa trial, BEOV (AKP-020), 20 mg, daily for 28 days, per os, in seven type 2 diabetic subjects, was associated with reductions in fasting blood glucose and %HbA1c; improved responses to oral glucose tolerance testing, versus the observed worsening of diabetic symptoms in the two placebo controls.
Publication: J. Inorg. Biochem. 2009 Apr ;103(4)::554-8. :doi: 10.1016/j.jinorgbio.2008.12.003.
Publication Date: 2009 Apr
Study Author(s): Thompson, Katherine H;Lichter, Jay;LeBel, Carl;Scaife, Michael C;McNeill, John H;Orvig, Chris;
Institution: Medicinal Inorganic Chemistry Group, Chemistry Department, 2036 Main Mall, University of British Columbia, Vancouver, BC, Canada. [email protected]
Shortcut link to this study:
Publication Date: 2009 Apr
Study Author(s): Thompson, Katherine H;Lichter, Jay;LeBel, Carl;Scaife, Michael C;McNeill, John H;Orvig, Chris;
Institution: Medicinal Inorganic Chemistry Group, Chemistry Department, 2036 Main Mall, University of British Columbia, Vancouver, BC, Canada. [email protected]
Shortcut link to this study:
3-Hydroxy-2-methyl-4-pyrone and 2-ethyl-3-hydroxy-4-pyrone (maltol and ethyl maltol, respectively) have proven especially suitable as ligands for vanadyl ions, in potential insulin enhancing agents for diabetes mellitus. Both bis(maltolato)oxovanadium(IV) (BMOV), and the ethylmaltol analog, bis(ethylmaltolato)oxovanadium(IV) (BEOV), have the desired intermediate stability for pro-drug use, and have undergone extensive pre-clinical testing for safety and efficacy. Pharmacokinetic evaluation indicates a pattern of biodistribution consistent with fairly rapid dissociation and uptake, binding to serum transferrin for systemic circulation and transport to tissues, with preferential uptake in bone. These bis-ligand oxovanadium(IV) (VOL(2)) compounds have a clear advantage over inorganic vanadyl sulfate in terms of bioavailability and pharmaceutical efficacy BEOV : has now completed Phase I and has advanced to Phase II clinical trials. In the Phase I trial, a range of doses from 10 mg to 90 mg BEOV, given orally to non-diabetic volunteers, resulted in no adverse effects; all biochemical parameters remained within normal limits. In the Phase IIa trial, BEOV (AKP-020), 20 mg, daily for 28 days, per os, in seven type 2 diabetic subjects, was associated with reductions in fasting blood glucose and %HbA1c; improved responses to oral glucose tolerance testing, versus the observed worsening of diabetic symptoms in the two placebo controls.
PMID: 19162329
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