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非达替尼 - 版本历史
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2026-01-08T08:26:24Z
<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>[[非达替尼]]([[Fedratinib]])</strong>，商品名为<strong>[[印瑞必]]([[Inrebic]])**，研发代码为**[[TG101348]]</strong>，是由[[百时美施贵宝]]([[BMS]])开发的一种强效、口服、高选择性的<strong>[[JAK2抑制剂]]</strong>。该药物主要用于治疗成人中危-2或高危的<strong>[[骨髓纤维化]]</strong>（包括原发性、真性红细胞增多症后及原发性血小板增多症后骨髓纤维化）。[[非达替尼]]通过精准阻断野生型及突变型（[[V617F]]）的 <strong>[[JAK2]]</strong> 激酶，有效抑制骨髓异常增生并缓解脾脏肿大。其作为[[芦可替尼]]进展后的关键二线选择，填补了骨髓纤维化治疗的重要空白，但需警惕严重的神经系统风险。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">非达替尼 (Fedratinib)</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Inrebic·JAK2抑制剂·点击展开</div><br />
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<div style="display: inline-block; background: #ffffff; border: 1px solid #e2e8f0; border-radius: 12px; padding: 15px; box-shadow: 0 4px 10px rgba(0,0,0,0.04);"><br />
<div style="width: 120px; height: 80px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.75em; padding: 10px; text-align: center;">Chemical Structure: C27H29N7O3S (Aminopyrimidine)</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 10px; font-weight: 600;">核心靶标：JAK2 / FLT3</div><br />
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<th style="text-align: left; padding: 6px 10px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[Entrez]]ID</th><br />
<td style="padding: 6px 10px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3717([[JAK2]])</td><br />
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<th style="text-align: left; padding: 6px 10px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]ID</th><br />
<td style="padding: 6px 10px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">6192</td><br />
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<th style="text-align: left; padding: 6px 10px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th><br />
<td style="padding: 6px 10px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">O60674</td><br />
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<th style="text-align: left; padding: 6px 10px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th><br />
<td style="padding: 6px 10px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">524.6g/mol</td><br />
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<th style="text-align: left; padding: 6px 10px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药途径</th><br />
<td style="padding: 6px 10px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">口服 (400mg QD)</td><br />
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<th style="text-align: left; padding: 6px 10px; background-color: #f1f5f9; color: #475569;">黑框警告</th><br />
<td style="padding: 10px; color: #b91c1c;">韦尼克脑病</td><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;">分子机制：选择性抑制 JAK2 与 FLT3</h2><br />
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[[非达替尼]]作为一种激酶抑制剂，其抗肿瘤逻辑主要集中在异常信号转导的截断上：<br />
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<li style="margin-bottom: 12px;"><strong>JAK2 激酶域竞争：</strong> 非达替尼以 ATP 竞争性方式结合 <strong>[[JAK2]]</strong> 的激酶结构域。它对 JAK2 的抑制活性显著高于 <strong>[[JAK1]]</strong>、<strong>[[JAK3]]</strong> 及 <strong>[[TYK2]]</strong>。通过阻断 [[JAK2/STAT3]] 和 [[JAK2/STAT5]] 磷酸化，抑制肿瘤细胞增殖。</li><br />
<li style="margin-bottom: 12px;"><strong>FLT3 旁路封锁：</strong> 该药物还具有针对 <strong>[[FLT3]]</strong>（FMS 样酪氨酸激酶 3）的活性，这有助于进一步削弱骨髓增殖性疾病中的细胞生存信号，特别是对携带 FLT3 异常的克隆具有潜在抑制作用。</li><br />
<li style="margin-bottom: 12px;"><strong>克服突变敏感性：</strong> 非达替尼不仅抑制野生型 JAK2，对骨髓纤维化中最常见的 <strong>[[V617F]]</strong> 突变体也表现出极高的亲和力。</li><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;">核心临床研究与获益矩阵</h2><br />
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<th style="padding: 10px; border: 1px solid #e2e8f0; text-align: left;">试验名称</th><br />
<th style="padding: 10px; border: 1px solid #e2e8f0; text-align: left;">研究人群</th><br />
<th style="padding: 10px; border: 1px solid #e2e8f0; text-align: left;">核心终点 (SVR35)</th><br />
<th style="padding: 10px; border: 1px solid #e2e8f0; text-align: left;">症状改善 (TSS50)</th><br />
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<td style="padding: 10px; border: 1px solid #e2e8f0; font-weight: 600;">[[JAKARTA]]</td><br />
<td style="padding: 10px; border: 1px solid #e2e8f0;">一线未治疗骨髓纤维化</td><br />
<td style="padding: 10px; border: 1px solid #e2e8f0; color: #1e40af;">37% 至 47%</td><br />
<td style="padding: 10px; border: 1px solid #e2e8f0;">36% 至 40%</td><br />
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<td style="padding: 10px; border: 1px solid #e2e8f0; font-weight: 600;">[[JAKARTA2]]</td><br />
<td style="padding: 10px; border: 1px solid #e2e8f0;">芦可替尼进展/不耐受</td><br />
<td style="padding: 10px; border: 1px solid #e2e8f0; color: #1e40af;">31%</td><br />
<td style="padding: 10px; border: 1px solid #e2e8f0;">27%</td><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;">诊疗策略：序贯应用与安全性闭环</h2><br />
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[[非达替尼]]的应用需严格遵循其特有的安全性监测路径：<br />
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<li style="margin-bottom: 12px;"><strong>二线挽救首选：</strong> 在 [[芦可替尼]] 治疗失败（如耐药或脾脏重新肿大）后，非达替尼是首选的转换方案。研究显示其可为芦可替尼经治患者提供进一步的脾脏回缩获益。</li><br />
<li style="margin-bottom: 12px;"><strong>硫胺素(维生素 B1)监测：</strong> 治疗启动前及过程中，必须监测血清硫胺素水平。若发现缺乏，需纠正后方可给药。</li><br />
<li style="margin-bottom: 12px;"><strong>风险管控：</strong> 必须警惕潜在的<strong>[[韦尼克脑病]]</strong>风险。若患者出现共济失调、眼肌麻痹或精神状态改变，应立即停药并补充硫胺素。</li><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;">关键相关概念</h2><br />
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<li style="margin-bottom: 8px;"><strong>[[JAK2 V617F]]：</strong> 骨髓增殖性肿瘤中最核心的致病突变，是非达替尼的主靶点。</li><br />
<li style="margin-bottom: 8px;"><strong>[[芦可替尼]]：</strong> 第一代 JAK1/2 抑制剂，非达替尼与其构成主要的竞争与序贯关系。</li><br />
<li style="margin-bottom: 8px;"><strong>[[韦尼克脑病]]：</strong> 曾导致非达替尼研发一度中止的严重副作用，现已建立标准化监测路径。</li><br />
<li style="margin-bottom: 8px;"><strong>[[莫普替尼]]([[Momelotinib]])：</strong> 另一类 JAK 抑制剂，侧重于缓解贫血及改善脾脏。</li><br />
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<span style="color: #0f172a; font-weight: bold; font-size: 1.05em; display: inline-block; margin-bottom: 10px;">学术参考文献与权威评审</span><br />
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[1] <strong>Pardanani A, Harrison C, et al. (2017/Updated).</strong> <em>Safety and Efficacy of Fedratinib in Myelofibrosis: A Phase III Randomised Study (JAKARTA).</em> <strong>[[JAMA Oncology]]</strong>.<br><br />
<span style="color: #475569;">[点评]：该项关键临床试验证明了非达替尼在显著缩小脾脏容积及减轻症状方面的有效性。</span><br />
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[2] <strong>[[The Lancet Haematology]]. (2023Revision).</strong> <em>Fedratinib in patients with myelofibrosis previously treated with ruxolitinib (JAKARTA2): a single-arm, open-label, phase 2 study.</em> [Academic Review]<br><br />
<span style="color: #475569;">[点评]：系统回顾了二线使用非达替尼的挽救价值及其安全性特征。</span><br />
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非达替尼 (Fedratinib) 诊疗生态 · 知识图谱<br />
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<td style="width: 80px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px; text-align: right;">关联靶点</td><br />
<td style="padding: 10px 15px;">[[JAK2]]•[[V617F突变]]•[[FLT3]]•[[STAT3]]•[[STAT5]]</td><br />
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<td style="width: 80px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px; text-align: right;">直接竞品</td><br />
<td style="padding: 10px 15px;">[[芦可替尼]]•[[莫普替尼]]•[[帕克替尼]]</td><br />
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<td style="width: 80px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px; text-align: right;">前沿驱动</td><br />
<td style="padding: 10px 15px;">[[外泌体精准递送研究]]•[[与BCL2抑制剂联合]]•[[低剂量维持策略]]•[[JAK2选择性优化]]</td><br />
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223.160.139.194