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阿亚替尼 - 版本历史
2026-04-18T03:40:52Z
本wiki的该页面的版本历史
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https://www.yiliao.com/index.php?title=%E9%98%BF%E4%BA%9A%E6%9B%BF%E5%B0%BC&diff=315527&oldid=prev
2026年1月23日 (五) 15:44 77921020
2026-01-23T15:44:29Z
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<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">←上一版本</td>
<td colspan="2" style="background-color: #fff; color: #202122; text-align: center;">2026年1月23日 (五) 15:44的版本</td>
</tr><tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l44" >第44行：</td>
<td colspan="2" class="diff-lineno">第44行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物类别</th></del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;">STAMP 抑制剂</td></del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"> </tr></del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div><del style="font-weight: bold; text-decoration: none;"> <tr></del></div></td><td colspan="2"> </td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">适应症</th></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">适应症</th></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">CML (≥3线), T315I 突变 CML</td></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">CML (≥3线), T315I 突变 CML</td></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l56" >第56行：</td>
<td colspan="2" class="diff-lineno">第52行：</td></tr>
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<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;"><del class="diffchange diffchange-inline">给药方式</del></th></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;"><ins class="diffchange diffchange-inline">给药途径</ins></th></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">口服 (BID <del class="diffchange diffchange-inline">或 QD)</del></td></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;"<ins class="diffchange diffchange-inline">><strong</ins>>口服<ins class="diffchange diffchange-inline"></strong> </ins>(<ins class="diffchange diffchange-inline">空腹: 餐前2h/餐后1h)</td></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> </tr></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <tr></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">参考剂量</th></ins></div></td></tr>
<tr><td colspan="2"> </td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div><ins class="diffchange diffchange-inline"> <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">常规: 80mg QD 或 40mg </ins>BID<ins class="diffchange diffchange-inline"><br>T315I: <strong>200mg BID</strong></ins></td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> </tr></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td></tr>
<tr><td colspan="2" class="diff-lineno" id="mw-diff-left-l102" >第102行：</td>
<td colspan="2" class="diff-lineno">第102行：</td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <tr></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">CML-CP (≥3线)</td></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">CML-CP (≥3线)</td></div></td></tr>
<tr><td class='diff-marker'>−</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #ffe49c; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1;">40mg BID 或 80mg QD</td></div></td><td class='diff-marker'>+</td><td style="color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #a3d3ff; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1;"<ins class="diffchange diffchange-inline">><strong</ins>>40mg BID<ins class="diffchange diffchange-inline"></strong> </ins>或 <ins class="diffchange diffchange-inline"><strong></ins>80mg QD<ins class="diffchange diffchange-inline"></strong></ins></td></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1;"></div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> <td style="padding: 10px; border: 1px solid #cbd5e1;"></div></td></tr>
<tr><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> 与 [[博舒替尼]] 相比：</div></td><td class='diff-marker'> </td><td style="background-color: #f8f9fa; color: #202122; font-size: 88%; border-style: solid; border-width: 1px 1px 1px 4px; border-radius: 0.33em; border-color: #eaecf0; vertical-align: top; white-space: pre-wrap;"><div> 与 [[博舒替尼]] 相比：</div></td></tr>
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77921020
https://www.yiliao.com/index.php?title=%E9%98%BF%E4%BA%9A%E6%9B%BF%E5%B0%BC&diff=315518&oldid=prev
77921020：建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面
2026-01-23T14:45:27Z
<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
<p><b>新页面</b></p><div><div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff; max-width: 1200px; margin: auto;"><br />
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<strong>阿亚替尼</strong>（Asciminib），商品名 <strong>Scemblix</strong>，是一种首创（First-in-Class）的<strong>STAMP抑制剂</strong>（Specifically Targeting the ABL Myristoyl Pocket，特异性靶向 ABL 肉豆蔻酰口袋）。与所有前代 ATP 竞争性 ABL1 抑制剂（如[[伊马替尼]]、[[达沙替尼]]）不同，阿亚替尼不结合激酶的 ATP 口袋，而是结合激酶结构域上的一个独特的<strong>变构位点</strong>（肉豆蔻酰口袋）。这种全新的机制使其能够模拟 ABL1 激酶的天然自我抑制状态，从而强效抑制 BCR-ABL1 的活性。临床上，阿亚替尼被批准用于治疗既往接受过至少两种 TKI 治疗的<strong>[[慢性粒细胞白血病]]</strong> (CML) 患者，以及携带 <strong>[[T315I]]</strong> 突变的 CML 患者。由于其独特的作用位点，它能克服大多数 ATP 位点的耐药突变，且副作用谱通常优于传统 TKI。<br />
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<div class="medical-infobox mw-collapsible mw-collapsed" style="width: 100%; max-width: 320px; margin: 0 auto 35px auto; border: 1.2px solid #bae6fd; border-radius: 12px; background-color: #ffffff; box-shadow: 0 8px 20px rgba(0,0,0,0.05); overflow: hidden;"><br />
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<div style="padding: 15px; color: #1e40af; background: linear-gradient(135deg, #e0f2fe 0%, #bae6fd 100%); text-align: center; cursor: pointer;"><br />
<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">Asciminib / 阿亚替尼</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">STAMP Allosteric Inhibitor (点击展开)</div><br />
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<div class="mw-collapsible-content"><br />
<div style="padding: 25px; text-align: center; background-color: #f8fafc;"><br />
<div style="display: inline-block; background: #ffffff; border: 1px solid #e2e8f0; border-radius: 12px; padding: 20px; box-shadow: 0 4px 10px rgba(0,0,0,0.04);"><br />
[[Image:Asciminib_mechanism_myristoyl_pocket_binding.png|100px|阿亚替尼结合肉豆蔻酰口袋]]<br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">变构抑制剂 / 克服T315I</div><br />
</div><br />
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<table style="width: 100%; border-spacing: 0; border-collapse: collapse; font-size: 0.85em;"><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">通用名</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Asciminib Hydrochloride</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">商品名</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Scemblix</td><br />
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<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">研发代号</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">ABL001</td><br />
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<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">449.8 g/mol</td><br />
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<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">核心靶点</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;"><strong>BCR-ABL1</strong> (变构位点)</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物类别</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;">STAMP 抑制剂</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">适应症</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">CML (≥3线), T315I 突变 CML</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">FDA批准</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2021年</td><br />
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<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药方式</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">口服 (BID 或 QD)</td><br />
</tr><br />
<tr><br />
<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">开发商</th><br />
<td style="padding: 6px 12px; color: #0f172a;">Novartis (诺华)</td><br />
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</table><br />
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阿亚替尼的作用机制是对 ABL1 激酶调控机制的精妙模仿，避开了拥挤的 ATP 结合位点。<br />
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<li style="margin-bottom: 12px;"><strong>肉豆蔻酰口袋 (Myristoyl Pocket)：</strong><br />
<br>正常的 ABL1 蛋白在其 N 端有一个肉豆蔻酰化修饰。这个疏水的肉豆蔻酰基团会插入到激酶结构域 C 叶的一个深口袋中，像“插销”一样锁定激酶，使其保持在<strong>自我抑制</strong>（Autoinhibited）的闭合构象。</li><br />
<li style="margin-bottom: 12px;"><strong>BCR-ABL1 的失控：</strong><br />
<br>在 BCR-ABL1 融合蛋白中，ABL1 丢失了 N 端的肉豆蔻酰化修饰，导致“插销”丢失，激酶构象开放，处于持续激活状态。</li><br />
<li style="margin-bottom: 12px;"><strong>STAMP 机制：</strong><br />
<br>阿亚替尼作为一种外源性分子，特异性地结合到这个空的<strong>肉豆蔻酰口袋</strong>中。它充当了丢失的“插销”，强迫 BCR-ABL1 激酶恢复到非活性的闭合构象。</li><br />
<li style="margin-bottom: 12px;"><strong>优势：</strong><br />
<br>由于不结合 ATP 口袋，阿亚替尼<strong>不受 ATP 结合位点突变（如 [[T315I]]）的影响</strong>。此外，它对其他激酶的脱靶效应极低，因此副作用通常比多靶点 TKI 更轻。</li><br />
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[[Image:Asciminib_allosteric_inhibition_vs_ATP_competitive.png|100px|阿亚替尼变构抑制与传统 ATP 竞争抑制的对比]]<br />
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<h2 style="background: #fff1f2; color: #9f1239; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #9f1239; font-weight: bold;">临床应用：ASCEMBL 研究</h2><br />
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<h3 style="margin-top: 0; color: #be123c; font-size: 1.1em;">后线治疗的新标准</h3><br />
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对于经历了多线 TKI 治疗失败、特别是因不耐受副作用而停药的 CML 患者，阿亚替尼提供了高效且低毒的新选择。<br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 20%;">适应症</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569; width: 30%;">给药方案</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床数据 (ASCEMBL)</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">CML-CP (≥3线)</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">40mg BID 或 80mg QD</td><br />
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与 [[博舒替尼]] 相比：<br />
<br>• <strong>MMR (24周)：</strong> 25.5% vs 13.2%<br />
<br>• <strong>因副作用停药率：</strong> 5.8% vs 21.1%<br />
<br>• 结论：疗效倍增，耐受性显著更优。<br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">T315I 突变 CML</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>200mg BID</strong> (高剂量)</td><br />
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针对 T315I 突变患者，阿亚替尼显示出与 [[普纳替尼]] 相当的活性，但没有普纳替尼严重的心血管/血栓风险。<br />
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<h2 style="background: #f1f5f9; color: #0f172a; padding: 10px 18px; border-radius: 0 6px 6px 0; font-size: 1.25em; margin-top: 40px; border-left: 6px solid #0f172a; font-weight: bold;">副作用与安全性</h2><br />
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阿亚替尼的安全性是其主要优势之一，这得益于其高度的靶点特异性。<br />
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<li style="margin-bottom: 12px;"><strong>常见不良反应：</strong><br />
<br>主要是 1-2 级的血小板减少、中性粒细胞减少、上呼吸道感染、肌肉骨骼疼痛。</li><br />
<li style="margin-bottom: 12px;"><strong>胰腺酶升高：</strong><br />
<br>无症状的<strong>淀粉酶和脂肪酶升高</strong>较常见，部分患者可能发生胰腺炎。需定期监测。</li><br />
<li style="margin-bottom: 12px;"><strong>心血管安全性：</strong><br />
<br>与普纳替尼相比，阿亚替尼的动脉闭塞事件（AOE）风险显著较低，使其成为有心血管高危因素患者的优选。</li><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 15px;">学术参考文献与权威点评</span><br />
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[1] <strong>Wylie AA, Schoepfer J, Jahnke W, et al. (2017).</strong> <em>The allosteric inhibitor ABL001 enables dual targeting of BCR–ABL1.</em> <strong>[[Nature]]</strong>. 2017;543(7647):733-737.<br><br />
<span style="color: #475569;">[发现之源]：基础研究奠基之作。首次描述了阿亚替尼（ABL001）结合肉豆蔻酰口袋的独特机制，并提出“双重抑制”（结合 ATP 抑制剂）可能彻底根除 CML 克隆的概念。</span><br />
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[2] <strong>Réa D, Mauro MJ, Boquimpani C, et al. (2021).</strong> <em>A Phase 3, Open-Label, Randomized Study of Asciminib, a STAMP Inhibitor, vs Bosutinib in CML After 2 or More Prior TKIs.</em> <strong>[[Blood]]</strong>. 2021;138(21):2031-2041.<br><br />
<span style="color: #475569;">[ASCEMBL 研究]：关键 III 期临床试验。证明了在多线治疗失败的 CML 患者中，阿亚替尼的疗效优于博舒替尼，且因副作用导致的停药率大幅降低，确立了其后线标准地位。</span><br />
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[3] <strong>Hughes TP, Mauro MJ, Cortes JE, et al. (2019).</strong> <em>Asciminib in Chronic Myeloid Leukemia after ABL Kinase Inhibitor Failure.</em> <strong>[[New England Journal of Medicine]]</strong>. 2019;381:2315-2326.<br><br />
<span style="color: #475569;">[I期临床]：首次人体试验，展示了阿亚替尼在重度预处理（包括对普纳替尼失败）患者中的安全性和有效性，特别是对 T315I 突变的活性。</span><br />
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[4] <strong>Schoepfer J, Jahnke W, Berellini G, et al. (2018).</strong> <em>Discovery of Asciminib (ABL001), an Allosteric Inhibitor of the Tyrosine Kinase Activity of BCR-ABL1.</em> <strong>[[Journal of Medicinal Chemistry]]</strong>. 2018;61(18):8120-8135.<br><br />
<span style="color: #475569;">[药物化学]：详细记录了从片段筛选到先导化合物优化，最终发现阿亚替尼的药物化学历程，突出了基于结构的药物设计（SBDD）的重要性。</span><br />
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阿亚替尼 · 知识图谱<br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">作用机制</td><br />
<td style="padding: 10px 15px; color: #334155;">[[STAMP]] • [[变构抑制]] • [[肉豆蔻酰口袋]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">适应症</td><br />
<td style="padding: 10px 15px; color: #334155;">[[CML]] (三线及以上) • [[T315I]] 突变</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">竞品/前代</td><br />
<td style="padding: 10px 15px; color: #334155;">[[普纳替尼]] (Ponatinib) • [[博舒替尼]] • [[伊马替尼]]</td><br />
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<td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">潜在策略</td><br />
<td style="padding: 10px 15px; color: #334155;">[[双重抑制]] (联合ATP竞争抑制剂) 以追求 TFR</td><br />
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