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char = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
char = p;code = 112
char = o;code = 111
char = i;code = 105
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = t;code = 116
char = a;code = 97
char = t;code = 116
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = c;code = 99
char = y;code = 121
char = s;code = 115
char = t;code = 116
char = e;code = 101
char = i;code = 105
char = n;code = 110
char = -;code = 45
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = T;code = 84
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = p;code = 112
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = n;code = 110
char = d;code = 100
char = o;code = 111
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = n;code = 110
char = e;code = 101
char = ;code = 32
char = n;code = 110
char = e;code = 101
char = o;code = 111
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = t;code = 116
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = ;code = 32
char = 2;code = 50
char = ;code = 32
char = (;code = 40
char = M;code = 77
char = E;code = 69
char = N;code = 78
char = 2;code = 50
char = );code = 41
char = ,;code = 44
char = ;code = 32
char = a;code = 97
char = ;code = 32
char = g;code = 103
char = r;code = 114
char = o;code = 111
char = u;code = 117
char = p;code = 112
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = f;code = 102
char = a;code = 97
char = m;code = 109
char = i;code = 105
char = l;code = 108
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = n;code = 110
char = c;code = 99
char = e;code = 101
char = r;code = 114
char = ;code = 32
char = s;code = 115
char = y;code = 121
char = n;code = 110
char = d;code = 100
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = z;code = 122
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = y;code = 121
char = ;code = 32
char = m;code = 109
char = e;code = 101
char = d;code = 100
char = u;code = 117
char = l;code = 108
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = h;code = 104
char = e;code = 101
char = o;code = 111
char = c;code = 99
char = h;code = 104
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = o;code = 111
char = c;code = 99
char = y;code = 121
char = t;code = 116
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = ,;code = 44
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = h;code = 104
char = y;code = 121
char = p;code = 112
char = e;code = 101
char = r;code = 114
char = p;code = 112
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = i;code = 105
char = a;code = 97
char = ;code = 32
char = a;code = 97
char = n;code = 110
char = d;code = 100
char = ;code = 32
char = g;code = 103
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = l;code = 108
char = i;code = 105
char = o;code = 111
char = n;code = 110
char = e;code = 101
char = u;code = 117
char = r;code = 114
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = t;code = 116
char = o;code = 111
char = s;code = 115
char = i;code = 105
char = s;code = 115
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = g;code = 103
char = a;code = 97
char = s;code = 115
char = t;code = 116
char = r;code = 114
char = o;code = 111
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = e;code = 101
char = r;code = 114
char = i;code = 105
char = c;code = 99
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = c;code = 99
char = o;code = 111
char = s;code = 115
char = a;code = 97
char = .;code = 46
char = ;code = 32
char = R;code = 82
char = e;code = 101
char = a;code = 97
char = r;code = 114
char = r;code = 114
char = a;code = 97
char = n;code = 110
char = g;code = 103
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = f;code = 102
char = o;code = 111
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 = R;code = 82
char = E;code = 69
char = T;code = 84
char = ;code = 32
char = (;code = 40
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 = ;code = 32
char = R;code = 82
char = E;code = 69
char = T;code = 84
char = /;code = 47
char = P;code = 80
char = T;code = 84
char = C;code = 67
char = );code = 41
char = ;code = 32
char = a;code = 97
char = r;code = 114
char = e;code = 101
char = ;code = 32
char = d;code = 100
char = e;code = 101
char = t;code = 116
char = e;code = 101
char = c;code = 99
char = t;code = 116
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = m;code = 109
char = a;code = 97
char = j;code = 106
char = o;code = 111
char = r;code = 114
char = i;code = 105
char = t;code = 116
char = y;code = 121
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = p;code = 112
char = i;code = 105
char = l;code = 108
char = l;code = 108
char = a;code = 97
char = r;code = 114
char = y;code = 121
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ;code = 32
char = c;code = 99
char = a;code = 97
char = r;code = 114
char = c;code = 99
char = i;code = 105
char = n;code = 110
char = o;code = 111
char = m;code = 109
char = a;code = 97
char = s;code = 115
char = ;code = 32
char = (;code = 40
char = P;code = 80
char = T;code = 84
char = C;code = 67
char = );code = 41
char = .;code = 46
char = ;code = 32
char = A;code = 65
char = t;code = 116
char = ;code = 32
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
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 = e;code = 101
char = u;code = 117
char = t;code = 116
char = i;code = 105
char = c;code = 99
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char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = t;code = 116
char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ;code = 32
char = a;code = 97
char = v;code = 118
char = a;code = 97
char = i;code = 105
char = l;code = 108
char = a;code = 97
char = b;code = 98
char = l;code = 108
char = e;code = 101
char = ;code = 32
char = f;code = 102
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = t;code = 116
char = h;code = 104
char = o;code = 111
char = l;code = 108
char = o;code = 111
char = g;code = 103
char = i;code = 105
char = e;code = 101
char = s;code = 115
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char = i;code = 105
char = s;code = 115
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = t;code = 116
char = o;code = 111
char = t;code = 116
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = p;code = 112
char = a;code = 97
char = r;code = 114
char = t;code = 116
char = i;code = 105
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = g;code = 103
char = i;code = 105
char = c;code = 99
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = e;code = 101
char = m;code = 109
char = o;code = 111
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = y;code = 121
char = r;code = 114
char = o;code = 111
char = i;code = 105
char = d;code = 100
char = ,;code = 44
char = ;code = 32
char = a;code = 97
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 = 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 = r;code = 114
char = a;code = 97
char = d;code = 100
char = i;code = 105
char = o;code = 111
char = -;code = 45
char = i;code = 105
char = o;code = 111
char = d;code = 100
char = i;code = 105
char = n;code = 110
char = e;code = 101
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
char = ;code = 32
char = o;code = 111
char = r;code = 114
char = ;code = 32
char = c;code = 99
char = h;code = 104
char = e;code = 101
char = m;code = 109
char = o;code = 111
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
char = :;code = 58
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char = d;code = 100
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = i;code = 105
char = t;code = 116
char = e;code = 101
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char = w;code = 119
char = i;code = 105
char = d;code = 100
char = e;code = 101
char = s;code = 115
char = p;code = 112
char = r;code = 114
char = e;code = 101
char = a;code = 97
char = d;code = 100
char = ;code = 32
char = u;code = 117
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = m;code = 109
char = u;code = 117
char = l;code = 108
char = t;code = 116
char = i;code = 105
char = m;code = 109
char = o;code = 111
char = d;code = 100
char = a;code = 97
char = l;code = 108
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = m;code = 109
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = u;code = 117
char = r;code = 114
char = v;code = 118
char = i;code = 105
char = v;code = 118
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = r;code = 114
char = a;code = 97
char = t;code = 116
char = e;code = 101
char = s;code = 115
char = ;code = 32
char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
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char = n;code = 110
char = o;code = 111
char = t;code = 116
char = ;code = 32
char = i;code = 105
char = m;code = 109
char = p;code = 112
char = r;code = 114
char = o;code = 111
char = v;code = 118
char = e;code = 101
char = d;code = 100
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char = m;code = 109
char = u;code = 117
char = c;code = 99
char = h;code = 104
char = ;code = 32
char = i;code = 105
char = n;code = 110
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char = t;code = 116
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char = e;code = 101
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char = a;code = 97
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char = t;code = 116
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char = e;code = 101
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char = c;code = 99
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char = e;code = 101
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char = i;code = 105
char = c;code = 99
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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 = s;code = 115
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char = t;code = 116
char = h;code = 104
char = a;code = 97
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char = t;code = 116
char = r;code = 114
char = e;code = 101
char = a;code = 97
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char = m;code = 109
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char = t;code = 116
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char = o;code = 111
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char = i;code = 105
char = o;code = 111
char = n;code = 110
char = s;code = 115
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char = s;code = 115
char = h;code = 104
char = o;code = 111
char = u;code = 117
char = l;code = 108
char = d;code = 100
char = ;code = 32
char = b;code = 98
char = e;code = 101
char = ;code = 32
char = e;code = 101
char = x;code = 120
char = p;code = 112
char = l;code = 108
char = o;code = 111
char = r;code = 114
char = e;code = 101
char = d;code = 100
char = .;code = 46
char = ;code = 32
char = S;code = 83
char = e;code = 101
char = v;code = 118
char = e;code = 101
char = r;code = 114
char = a;code = 97
char = l;code = 108
char = ;code = 32
char = s;code = 115
char = m;code = 109
char = a;code = 97
char = l;code = 108
char = l;code = 108
char = -;code = 45
char = m;code = 109
char = o;code = 111
char = l;code = 108
char = e;code = 101
char = c;code = 99
char = u;code = 117
char = l;code = 108
char = e;code = 101
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char = i;code = 105
char = n;code = 110
char = h;code = 104
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
char = ;code = 32
char = o;code = 111
char = f;code = 102
char = ;code = 32
char = R;code = 82
char = E;code = 69
char = T;code = 84
char = ;code = 32
char = k;code = 107
char = i;code = 105
char = n;code = 110
char = a;code = 97
char = s;code = 115
char = e;code = 101
char = ;code = 32
char = a;code = 97
char = c;code = 99
char = t;code = 116
char = i;code = 105
char = v;code = 118
char = i;code = 105
char = t;code = 116
char = y;code = 121
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char = h;code = 104
char = a;code = 97
char = v;code = 118
char = e;code = 101
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char = b;code = 98
char = e;code = 101
char = e;code = 101
char = n;code = 110
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char = d;code = 100
char = e;code = 101
char = s;code = 115
char = c;code = 99
char = r;code = 114
char = i;code = 105
char = b;code = 98
char = e;code = 101
char = d;code = 100
char = ;code = 32
char = i;code = 105
char = n;code = 110
char = ;code = 32
char = t;code = 116
char = h;code = 104
char = e;code = 101
char = ;code = 32
char = l;code = 108
char = a;code = 97
char = s;code = 115
char = t;code = 116
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char = d;code = 100
char = e;code = 101
char = c;code = 99
char = a;code = 97
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char = e;code = 101
char = ,;code = 44
char = ;code = 32
char = s;code = 115
char = o;code = 111
char = m;code = 109
char = e;code = 101
char = ;code = 32
char = o;code = 111
char = f;code = 102
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 = c;code = 99
char = u;code = 117
char = r;code = 114
char = r;code = 114
char = e;code = 101
char = n;code = 110
char = t;code = 116
char = l;code = 108
char = y;code = 121
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 = i;code = 105
char = n;code = 110
char = g;code = 103
char = ;code = 32
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 = 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 = 46
char = ;code = 32
char = H;code = 72
char = e;code = 101
char = r;code = 114
char = e;code = 101
char = ,;code = 44
char = ;code = 32
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result sql = RET (Rearranged during Transfection) is a transmembrane tyrosine kinase expressed in central and peripheral nervous system and neural crest-derived cells and acts as a co-receptor of GDNF family neurotrophic factor in complex with GRFα family proteins. RET protein comprises an extracellular portion with four cadherine-like domains and a cysteine- rich region important for intermolecular interactions; a hydrophobic transmembrane domain; an intracellular part comprising the juxtamembrane domain with regulatory function and the catalytic domain that phosphorylates the tyrosine residues of substrates. RET is involved in the development of enteric nervous system and renal organogenesis during embryonic life. Mutations of RET are associated to a subset of colorectal cancer and are commonly found in hereditary and sporadic thyroid cancer. Activating point mutations in the cystein-rich or the kinase domain of RET cause multiple endocrine neoplasia type 2 (MEN2), a group of familial cancer syndromes characterized by medullary thyroid carcinoma, pheochromocytoma, parathyroid hyperplasia and ganglioneuromatosis of the gastroenteric mucosa. Rearranged forms of RET (termed RET/PTC) are detected in the majority of papillary thyroid carcinomas (PTC). At present, the therapeutic treatment available for these pathologies is the total or partial surgical removal of thyroid, associated with radio-iodine therapy or chemotherapy: despite widespread use of multimodality treatment, survival rates have not improved much in the past few decades, which suggests that new treatment options should be explored. Several small-molecule inhibitors of RET kinase activity have been described in the last decade, some of which are currently undergoing clinical evaluation. Here, I review the large preclinical effort to the development of specific RET inhibitors, including medicinal chemistry analyses that may help refine potency and selectivity of future RET-targeted inhibitors.
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char = n;code = 110
char = t;code = 116
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char = R;code = 82
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char = T;code = 84
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char = i;code = 105
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char = a;code = 97
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char = y;code = 121
char = .;code = 46
result sql = Development of RET kinase inhibitors for targeted cancer therapy.
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result sql = RET (Rearranged during Transfection) is a transmembrane tyrosine kinase expressed in central and peripheral nervous system and neural crest-derived cells and acts as a co-receptor of GDNF family neurotrophic factor in complex with GRFα family proteins. RET protein comprises an extracellular portion with four cadherine-like domains and a cysteine- rich region important for intermolecular interactions; a hydrophobic transmembrane domain; an intracellular part comprising the juxtamembrane domain with regulatory function and the catalytic domain that phosphorylates the tyrosine residues of substrates. RET is involved in the development of enteric nervous system and renal organogenesis during embryonic life. Mutations of RET are associated to a subset of colorectal cancer and are commonly found in hereditary and sporadic thyroid cancer. Activating point mutations in the cystein-rich or the kinase domain of RET cause multiple endocrine neoplasia type 2 (MEN2), a group of familial cancer syndromes characterized by medullary thyroid carcinoma, pheochromocytoma, parathyroid hyperplasia and ganglioneuromatosis of the gastroenteric mucosa. Rearranged forms of RET (termed RET/PTC) are detected in the majority of papillary thyroid carcinomas (PTC). At present, the therapeutic treatment available for these pathologies is the total or partial surgical removal of thyroid, associated with radio-iodine therapy or chemotherapy: despite widespread use of multimodality treatment, survival rates have not improved much in the past few decades, which suggests that new treatment options should be explored. Several small-molecule inhibitors of RET kinase activity have been described in the last decade, some of which are currently undergoing clinical evaluation. Here, I review the large preclinical effort to the development of specific RET inhibitors, including medicinal chemistry analyses that may help refine potency and selectivity of future RET-targeted inhibitors.
Publication: Curr. Med. Chem. 2011 ;18(2)::162-75.
Publication Date: 2011
Study Author(s): Mologni, L;
Institution: Dept. Clinical Medicine and Prevention, University of Milano-Bicocca, Via Cadore 48, 20052 Monza, Italy. [email protected]
Shortcut link to this study:
Publication Date: 2011
Study Author(s): Mologni, L;
Institution: Dept. Clinical Medicine and Prevention, University of Milano-Bicocca, Via Cadore 48, 20052 Monza, Italy. [email protected]
Shortcut link to this study:
RET (Rearranged during Transfection) is a transmembrane tyrosine kinase expressed in central and peripheral nervous system and neural crest-derived cells and acts as a co-receptor of GDNF family neurotrophic factor in complex with GRFα family proteins. RET protein comprises an extracellular portion with four cadherine-like domains and a cysteine- rich region important for intermolecular interactions; a hydrophobic transmembrane domain; an intracellular part comprising the juxtamembrane domain with regulatory function and the catalytic domain that phosphorylates the tyrosine residues of substrates. RET is involved in the development of enteric nervous system and renal organogenesis during embryonic life. Mutations of RET are associated to a subset of colorectal cancer and are commonly found in hereditary and sporadic thyroid cancer. Activating point mutations in the cystein-rich or the kinase domain of RET cause multiple endocrine neoplasia type 2 (MEN2), a group of familial cancer syndromes characterized by medullary thyroid carcinoma, pheochromocytoma, parathyroid hyperplasia and ganglioneuromatosis of the gastroenteric mucosa. Rearranged forms of RET (termed RET/PTC) are detected in the majority of papillary thyroid carcinomas (PTC). At present, the therapeutic treatment available for these pathologies is the total or partial surgical removal of thyroid, associated with radio-iodine therapy or chemotherapy: despite widespread use of multimodality treatment, survival rates have not improved much in the past few decades, which suggests that new treatment options should be explored. Several small-molecule inhibitors of RET kinase activity have been described in the last decade, some of which are currently undergoing clinical evaluation. Here, I review the large preclinical effort to the development of specific RET inhibitors, including medicinal chemistry analyses that may help refine potency and selectivity of future RET-targeted inhibitors.
PMID: 21110809
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