選択的エストロゲン受容体修飾薬
参考資料

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↑  “Senshio (ospemifene)”.   The European Medicines Agency (EMA). 2015年11月2日閲覧。
↑  “Fareston”.   European Medicines Agency (EMA). 2015年11月2日閲覧。
↑  “Fablyn”.   The European Medicines Agency (EMA). 2015年11月2日閲覧。
ERαおよびERβのドメイン構造。リガンド非依存性制御に関与する既知のリン酸化部位の一部を含む。
エストロゲン受容体の作動薬および遮断薬の作用機構の構造的機序：エストロゲン受容体のリガンド結合ドメイン（LBD：緑色）と、作動薬のジエチルスチルベストロール（上、PDB: 3ERD​）または遮断薬の4-ヒドロキシタモキシフェン（下、3ERT​）との複合体の構造。リガンドは空間を埋める球体（白は炭素、赤は酸素）として描かれている。核内受容体に作動薬が結合すると、LBDのC末端のαヘリックス（H12：水色）は、LBDの表面に補助活性化因子タンパク質（赤色）が結合できるように配置される。ここで示されているのは、補助活性化因子タンパク質のほんの一部で、LXXLLアミノ酸配列モチーフを含むNRボックスと呼ばれる部分である。遮断薬は、核内受容体の同じリガンド結合腔を占有する。しかし、遮断薬のリガンドには長い側鎖があり、これが立体的にH12を変位させて、補助活性化因子が結合する空間とほぼ同じ位置を占める。そのため、LBDへの補助活性化因子の結合が阻害される。
4-ヒドロキシタモキシフェン(赤)と17β-エストラジオール(黒)の構造式
ステロイド骨格
トランス型(上)・シス型(下) クロミフェンの構造式
タモキシフェンの構造式
トレミフェンの構造式
ラロキシフェンは、ベンゾチオフェン基(赤)を持ち、フェニル4-ピペリジノエトキシ側鎖(緑)と柔軟なカルボニルヒンジで繋がっている。
ジヒドロナフタレン骨格(赤)を有するナフォキシジンの構造式
ラソフォキシフェンの化学構造。フェニル基がシス型に配置している。
バゼドキシフェンは、インドール骨格(赤)がベンジルオキシエチル鎖(緑)を介してアミンと結合している。
オスペミフェンの化学構造。エトキシ鎖の末端が、第1世代のSERMのようなジメチルアミノ基ではなく、ヒドロキシ基(赤)になっている。
ステロイドのABCD環（17β-エストラジオール）
ラロシキフェン構造中のステロイドA環・D環相当部分
SERMの発売時期（米国）