查看“波齐替尼”的源代码

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            <strong>[[波齐替尼]]</strong>（<strong>[[Poziotinib]]</strong>），研发代码为 <strong>[[HM781-36B]]</strong>，最初由韩国 <strong>[[韩美药品]]</strong> 研发，后由 <strong>[[Spectrum Pharmaceuticals]]</strong> 进行全球临床开发。该药是一种口服的、不可逆的 <strong>[[泛HER抑制剂]]</strong>，能够高度选择性地结合 <strong>[[EGFR]]</strong>、<strong>[[HER2]]</strong> 和 <strong>[[HER4]]</strong>。由于其分子结构紧凑，<strong>[[波齐替尼]]</strong> 能够突破因 <strong>[[20号外显子插入突变]]</strong> 导致的激酶域空间受限，实现对难治性 <strong>[[非小细胞肺癌]]</strong>（<strong>[[NSCLC]]</strong>）的靶向抑制。进入 2026 年，虽然面临 <strong>[[舒沃替尼]]</strong> 和 <strong>[[埃万妥单抗]]</strong> 等强效药物的竞争，但其在 <strong>[[HER2]]</strong> 插入突变领域的分子探索仍具有重要的临床参考价值。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">波齐替尼 (Poziotinib)</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">HM781-36B · Pan-HER TKI</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px;">核心靶点：<strong>[[泛HER]]</strong> / <strong>[[Exon20ins]]</strong></div>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%; font-weight: normal;"><strong>[[Entrez]]</strong>ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1956 / 2064</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;"><strong>[[HGNC]]</strong>ID</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3236 / 4830</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;"><strong>[[UniProt]]</strong></th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P00533 / P04626</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;">分子量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">486.35 g/mol</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;">给药途径</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">口服 (Oral)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; font-weight: normal;">研发厂家</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;"><strong>[[韩美药品]]</strong> / <strong>[[Spectrum]]</strong></td>
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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;">分子机制：空间受限下的共价锁定</h2>
    
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        <strong>[[波齐替尼]]</strong> 的药理优势在于其针对特定蛋白构象的几何适配能力：
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        <li style="margin-bottom: 12px;">构象适配：<strong>[[20号外显子插入突变]]</strong> 导致激酶域的 C 螺旋向内推移，显著缩小了 ATP 结合口袋。<strong>[[波齐替尼]]</strong> 较小的分子体积使其能够顺畅进入受限空间，与突变蛋白紧密结合。</li>
        <li style="margin-bottom: 12px;">不可逆阻断：通过其活性基团与 <strong>[[EGFR]]</strong>/<strong>[[HER2]]</strong> 激酶域结合位点附近的半胱氨酸残基形成共价键，产生持久的信号阻断作用。</li>
        <li style="margin-bottom: 12px;">多受体覆盖：作为 <strong>[[泛HER抑制剂]]</strong>，它能同时下调 <strong>[[PI3K]]</strong>/<strong>[[AKT]]</strong> 和 <strong>[[MEK]]</strong>/<strong>[[ERK]]</strong> 信号通路，多维度抑制肿瘤生长。</li>
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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%; font-weight: bold;">试验队列</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569; font-weight: bold;">目标突变亚型</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af; font-weight: bold;">关键有效性数据</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1;"><strong>[[ZENITH20-1]]</strong></td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;"><strong>[[EGFR]]</strong> <strong>[[Exon20ins]]</strong> (经治)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">ORR 约 14.8%，缓解持续时间受限。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1;"><strong>[[ZENITH20-2]]</strong></td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;"><strong>[[HER2]]</strong> <strong>[[Exon20ins]]</strong> (经治)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">ORR 达 27.8%，mPFS 约为 5.5 个月。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1;">主要毒性</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;" colspan="2;">常见 3 级以上 <strong>[[皮疹]]</strong> (约 28%) 及 <strong>[[腹泻]]</strong> (约 26%)。</td>
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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;">诊疗策略：毒性防控与个体化剂量</h2>
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        鉴于 <strong>[[波齐替尼]]</strong> 的窄治疗窗口，2026 年临床应用指南强调精细化的剂量调控策略：
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        <li style="margin-bottom: 12px;">预防性皮肤护理：由于对野生型 EGFR 的强力抑制，<strong>[[皮疹]]</strong> 发生率极高。建议在治疗首周即开始使用局部糖皮质激素和润肤剂预防。</li>
        <li style="margin-bottom: 12px;">剂量调整路径：推荐起始剂量为 16mg QD，但对于耐受性差的患者，临床常采用 8mg BID 或 12mg QD 的调整方案以维持治疗强度。</li>
        <li style="margin-bottom: 12px;">靶点轮替决策：在 <strong>[[埃万妥单抗]]</strong> 或 <strong>[[舒沃替尼]]</strong> 治疗进展后，若患者仍携带 <strong>[[Exon20ins]]</strong> 且无其他旁路激活，波齐替尼可作为后线探索性选择。</li>
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            <li style="margin-bottom: 8px;"><strong>[[Exon20ins]]</strong>：<strong>[[非小细胞肺癌]]</strong> 中一类具有高度空间异质性的难治突变。</li>
            <li style="margin-bottom: 8px;"><strong>[[泛HER抑制剂]]</strong>：能够同时封锁整个 HER 受体家族信号传导的药物类别。</li>
            <li style="margin-bottom: 8px;"><strong>[[舒沃替尼]]</strong>：该领域目前的全球领先国产口服 <strong>[[TKI]]</strong>。</li>
            <li style="margin-bottom: 8px;"><strong>[[不可逆结合]]</strong>：通过共价键增强药物与靶蛋白结合时长的一种生物化学策略。</li>
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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>
        
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            [1] Le X, et al. (2022). <strong>[[Poziotinib]]</strong> in Patients With <strong>[[HER2]]</strong> Exon 20 Insertion–Positive <strong>[[Metastatic NSCLC]]</strong>: Results From ZENITH20-2. <strong>[[Journal of Clinical Oncology]]</strong>.
            <br><span style="color: #475569;">[权威点评]：该项二期研究证实了其在 <strong>[[HER2]]</strong> 亚型中的疗效显著优于传统化疗。</span>
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            [2] Heymach JV, et al. (2021). <strong>[[Poziotinib]]</strong> for Patients with <strong>[[HER2]]</strong> Exon 20 Insertions: A Next-Generation Challenge. <strong>[[Cancer Cell]]</strong>.[Academic Review]
            <br><span style="color: #475569;">[学术点评]：深度解析了该药在分子动力学模拟下对抗 20 外显子插入突变的结构生物学机制。</span>
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            波齐替尼 (Poziotinib) 诊疗生态 · 知识图谱
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">关联靶点</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[EGFR]]</strong>•<strong>[[HER2]]</strong>•<strong>[[HER4]]</strong>•<strong>[[Exon20ins]]</strong>•<strong>[[Cys797]]</strong></td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">行业竞争</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[舒沃替尼]]</strong>•<strong>[[莫博替尼]]</strong>•<strong>[[埃万妥单抗]]</strong>•<strong>[[奥希替尼]]</strong></td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">战略实体</td>
                <td style="padding: 10px 15px; color: #334155;"><strong>[[韩美药品]]</strong>•<strong>[[Spectrum]]</strong>•<strong>[[FDA]]</strong>•<strong>[[NMPA]]</strong>•<strong>[[NCCN指南]]</strong></td>
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                <td style="width: 85px; background-color: #f8fafc; color: #334155; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">前沿探索</td>
                <td style="padding: 10px 15px; color: #334155;">针对 <strong>[[脑转移]]</strong> 的改型研究•联合 <strong>[[抗血管生成]]</strong> 药物•针对 <strong>[[罕见HER2突变]]</strong> 的跨瘤种应用•给药周期优化</td>
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