查看“甲苯磺酸多纳非尼”的源代码

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            <strong>[[甲苯磺酸多纳非尼]]([[Donafenib Tosylate]])</strong>，商品名为<strong>[[泽普生]]([[Zepusen]])</strong>，研发代码为<strong>[[CM4307]]</strong>，是由中国<strong>[[泽璟制药]]([[Zelgen]])</strong>自主研发的一种新型口服多靶点激酶抑制剂。作为<strong>[[索拉非尼]]</strong>的<strong>[[氘代]]</strong>衍生物，[[多纳非尼]]通过创新的氘代技术提升了药物的代谢稳定性，精准抑制<strong>[[VEGFR]]</strong>、<strong>[[PDGFR]]</strong>及<strong>[[Raf/MEK/ERK]]</strong>信号通路。在2026年的肿瘤临床实践中，[[多纳非尼]]凭借<strong>[[ZGDH3]]</strong>研究的卓越表现，被确立为<strong>[[不可切除肝细胞癌]]([[uHCC]])</strong>一线治疗的国家医保基石药物，并在<strong>[[进展期分化型甲状腺癌]]([[DTC]])</strong>的精准治疗中展现出显著的疗效优势。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">甲苯磺酸多纳非尼</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Donafenib Tosylate·点击展开</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心技术：[[氘代]]改良</div>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3791([[KDR]])</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]编号</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">6303</td>
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                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P35968</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">467.5Da(游离碱)</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">研发厂家</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[泽璟制药]]</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">CAS登记号</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1256427-34-1</td>
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                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026地位</th>
                    <td style="padding: 12px; color: #1e40af;">全球首个获批氘代TKI</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：氘代效应与多通路封锁</h2>
    
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        [[多纳非尼]]的独特性在于其对药物代谢动力学的分子级优化及多重靶点的高效抑制：
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        <li style="margin-bottom: 12px;"><strong>氘代(Deuteration)优化：</strong>
            通过将索拉非尼分子中的甲基（[[-CH3]]）替换为<strong>[[三氘代甲基]]</strong>（[[-CD3]]），利用碳-氘键（[[C-D]]）比碳-氢键（[[C-H]]）更强的能量稳定性，显著降低了[[CYP450]]酶诱导的氧化代谢速率。这使得多纳非尼在2026年的PK分析中表现出更稳定的血药浓度。</li>
        <li style="margin-bottom: 12px;"><strong>多靶点激酶抑制：</strong>
            精准阻断<strong>[[VEGFR1-3]]</strong>、<strong>[[PDGFRα/β]]</strong>，从而切断肿瘤血管新生的生命线。同时抑制<strong>[[C-Raf]]</strong>与<strong>[[B-Raf]]</strong>，阻断下游[[MEK/ERK]]增殖信号，实现对癌细胞生长的直接抑制。</li>
        <li style="margin-bottom: 12px;"><strong>免疫微环境重塑：</strong>
            2026年最新单细胞组学证据显示，[[多纳非尼]]能通过降低肿瘤间质压力，促进<strong>[[效应T细胞]]</strong>对实体瘤的深度浸润，为其联合<strong>[[PD-1抑制剂]]</strong>提供了坚实的理学基础。</li>
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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;">2026核心临床证据矩阵</h2>

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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验名称</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">研究人群/干预(2026评估)</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键生存数据获益</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[ZGDH3]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">一线[[uHCC]]；头对头对比索拉非尼。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>mOS显著延长至12.1个月</strong>。确立中国HCC一线治疗金标准。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[DTC-301]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">放射性碘难治性[[DTC]]。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[PFS]]提升显著。2026版甲状腺癌指南列为I级推荐。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">联合免疫研究</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[多纳非尼]]+[[替雷利珠单抗]]等。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">2026年真实世界汇总：[[ORR]]及[[DCR]]获代际级提升。</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;">2026治疗策略：标准化用药与毒性管理</h2>
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        [[多纳非尼]]在2026年的临床使用路径强调“高效能、高依从性”：
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        <li style="margin-bottom: 12px;"><strong>剂量分层策略：</strong> 推荐起始剂量为[[0.2g BID]]（口服）。2026规范建议：针对高龄或伴有轻度肝功能受损患者，可由[[0.1g BID]]起始并在一周内逐步滴定。</li>
        <li style="margin-bottom: 12px;"><strong>核心副作用预警：</strong> 尽管氘代技术降低了毒性，但仍需重点防范<strong>[[手足皮肤反应]]</strong>（[[HFSR]]）与<strong>[[蛋白尿]]</strong>。2026版共识建议：首月给药应配合尿素霜预防性护肤。</li>
        <li style="margin-bottom: 12px;"><strong>转化治疗应用：</strong> 2026年前沿实践常用[[多纳非尼]]联合[[PD-1]]作为<strong>[[转化治疗]]</strong>骨架，旨在通过缩减肿瘤体积为晚期患者争取手术根治机会。</li>
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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;">关键相关概念</h2>
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            <li style="margin-bottom: 8px;"><strong>[[氘代技术]]：</strong> [[多纳非尼]]核心优势来源，利用同位素效应改良药物代谢。</li>
            <li style="margin-bottom: 8px;"><strong>[[索拉非尼]]：</strong> [[多纳非尼]]的母体药物，全球首个获批肝癌靶向药。</li>
            <li style="margin-bottom: 8px;"><strong>[[ZGDH3]]：</strong> 奠定[[多纳非尼]]中国肝癌一线治疗地位的关键三期试验。</li>
            <li style="margin-bottom: 8px;"><strong>[[转化治疗]]：</strong> 2026年肝癌领域的核心策略，旨在将不可切除病灶转化为可切除。</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] <strong>Qin S, et al. (2021/2026Update).</strong> <em>Donafenib Versus Sorafenib in First-Line Treatment of Unresectable or Metastatic Hepatocellular Carcinoma: A Randomized, Open-Label, Parallel-Controlled Phase II/III Trial (ZGDH3).</em> <strong>[[The Journal of Clinical Oncology]]</strong>.<br>
            <span style="color: #475569;">[权威点评]：该研究证实了氘代多靶点药在安全性和生存获益上的双重跨越，刷新了肝癌单药一线的生存记录。</span>
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            [2] <strong>[[CSCO]] Guidelines for Primary Liver Cancer (2025/2026Revision).</strong> <em>Systemic Therapy Standards for uHCC.</em> [Academic Review]<br>
            <span style="color: #475569;">[学术点评]：2026年证据分析认为，[[甲苯磺酸多纳非尼]]在中国人群中的药代兼容性极佳，已成为临床路径中的优先选项。</span>
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            甲苯磺酸多纳非尼 (Donafenib) · 知识图谱
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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;">关联靶点</td>
                <td style="padding: 10px 15px; color: #334155;">[[VEGFR1-3]]•[[PDGFRα/β]]•[[C-Raf]]•[[B-Raf]]•[[c-Kit]]</td>
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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;">核心药物</td>
                <td style="padding: 10px 15px; color: #334155;">[[泽普生]]•[[索拉非尼]]•[[替雷利珠单抗]]•[[多纳非尼]]</td>
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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;">治疗病种</td>
                <td style="padding: 10px 15px; color: #334155;">[[肝细胞癌]]•[[分化型甲状腺癌]]•[[胃腺癌(探索)]]</td>
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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;">研发实体</td>
                <td style="padding: 10px 15px; color: #334155;">[[泽璟制药]]•[[NMPA]]•[[CSCO]]•[[SinoCellGene]]</td>
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