Modulation of Gamma-Secretase for the Treatment of Alzheimer's Disease

<table class="table-group" id="tab2"><tr><td><table class="table"><tr><td class="thead-hr" colspan="5"><hr/></td></tr><tr class="thead"><td align="left"> </td><td align="center">E-2012</td><td align="center">JNJ-40418677</td><td align="center">GSM1</td><td align="center">SPI-1810</td></tr><tr><td class="thead-hr" colspan="5"><hr/></td></tr><tr><td align="left"><i>In vitro</i> A<svg height="17.262501" id="M10" style="vertical-align:-4.0404pt" version="1.1" viewbox="0 0 22.049999 17.262501" width="22.049999" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
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</svg> IC<sub>50</sub> (nM) CHO-2B7 cells</td><td align="center">33</td><td align="center">172</td><td align="center">62</td><td align="center">114</td></tr><tr><td align="left">Plasma exposure (<svg height="12.175" id="M11" style="vertical-align:-3.56265pt" version="1.1" viewbox="0 0 9.5625 12.175" width="9.5625" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
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</svg>M)</td><td align="center">4923</td><td align="center">7764</td><td align="center">2744</td><td align="center">14638</td></tr><tr><td align="left">Plasma fold over A<svg height="17.262501" id="M12" style="vertical-align:-4.0404pt" version="1.1" viewbox="0 0 22.049999 17.262501" width="22.049999" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
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t-62 25.5q-24 0 -43.5 -9t-35 -29.5t-27 -44t-22.5 -63t-19.5 -75.5t-18.5 -91q-57 -294 -68 -380q-26 -190 -35 -200q-26 -31 -97 -37l-4 26q19 9 48 170l77 413q23 121 52.5 187.5t83.5 114.5q70 62 148 62q51 0 88.5 -34t37.5 -91z" id="x1D6FD"></path></g>
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</svg> IC<sub>50</sub> for 25% reduction</td><td align="center">149</td><td align="center">45</td><td align="center">44</td><td align="center">128</td></tr><tr><td align="left">Brain exposure (<svg height="12.175" id="M13" style="vertical-align:-3.56265pt" version="1.1" viewbox="0 0 9.5625 12.175" width="9.5625" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
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</svg>M)</td><td align="center">2749</td><td align="center">7497</td><td align="center">8681</td><td align="center">20368</td></tr><tr><td align="left">Brain fold over A<svg height="17.262501" id="M14" style="vertical-align:-4.0404pt" version="1.1" viewbox="0 0 22.049999 17.262501" width="22.049999" xmlns="http://www.w3.org/2000/svg" xmlns:xlink="http://www.w3.org/1999/xlink">
<g transform="matrix(.017,-0,0,-.017,.062,12.162)"><path d="M558 587q0 -32 -14 -61t-40 -53.5t-48.5 -41t-54.5 -36.5q144 -51 144 -174q0 -55 -43.5 -108t-104.5 -87q-77 -42 -131 -42q-31 0 -54 20t-31 47l11 18q48 -29 108 -29q79 0 119.5 43t40.5 109t-44.5 107.5t-119.5 50.5l22 47q34 1 65 21q96 61 96 157q0 42 -24 67.5
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<g transform="matrix(.012,-0,0,-.012,9.938,17.2)"><path d="M456 178h-96v-72q0 -51 12.5 -62.5t72.5 -16.5v-27h-256v27q65 5 78 17t13 62v72h-260v28q182 271 300 426h40v-407h96v-47zM280 225v295h-2q-107 -148 -196 -295h198z" id="x34"></path></g><g transform="matrix(.012,-0,0,-.012,15.649,17.2)"><path d="M412 140l28 -9q0 -2 -35 -131h-373v23q112 112 161 170q59 70 92 127t33 115q0 63 -31 98t-86 35q-75 0 -137 -93l-22 20l57 81q55 59 135 59q69 0 118.5 -46.5t49.5 -122.5q0 -62 -29.5 -114t-102.5 -130l-141 -149h186q42 0 58.5 10.5t38.5 56.5z" id="x32"></path></g>
</svg> IC<sub>50</sub> for 25% reduction</td><td align="center">83</td><td align="center">44</td><td align="center">140</td><td align="center">179</td></tr><tr class="table-tr"><td colspan="5"><hr class="tbody-hr"/></td></tr></table></td></tr></table>

GSM potency versus plasma exposure in mice.

International Journal of Alzheimer’s Disease

tab2

Table 2

Table 2: Modulation of Gamma-Secretase for the Treatment of Alzheimer's Disease 