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Gilteritinib - 版本历史
2026-04-18T13:25:46Z
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2026-01-16T02:55:01Z
<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>
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<strong>[[吉列替尼]]</strong>（<strong>[[Gilteritinib]]</strong>，商品名：<strong>[[适加坦]]</strong>/<strong>[[Xospata]]</strong>）是一种创新的、高选择性的口服<strong>[[FLT3]]</strong>和<strong>[[AXL]]</strong>激酶抑制剂。作为一种<strong>[[I型抑制剂]]</strong>，它能够同时针对<strong>[[FLT3-ITD]]</strong>（内部串联重复）和<strong>[[FLT3-TKD]]</strong>（激酶结构域突变）发挥强效抑制作用。[[吉列替尼]]的临床意义在于其打破了复发或难治性（[[R/R]]）[[FLT3]]突变型<strong>[[急性髓系白血病]]</strong>（[[AML]]）缺乏有效靶向药的困境。此外，由于其具备抑制[[AXL]]激酶的能力，该药物能有效延缓因[[AXL]]激活介导的获得性耐药，显著延长患者的[[总生存期]]。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[吉列替尼]]</div><br />
<div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[Gilteritinib]] / [[ASP2215]] · 点击展开</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[FLT3]] (ITD/TKD) & [[AXL]]</div><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 45%;">[[Entrez]]ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">2322([[FLT3]])</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3765</td><br />
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<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P36888</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物类型</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[I型酪氨酸激酶抑制剂]]</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子量]]</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">552.71Da</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">原研厂商</th><br />
<td style="padding: 12px; color: #0f172a;">[[Astellas]] (安斯泰来)</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：多靶位阻断与耐药逆转</h2><br />
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[[吉列替尼]]通过竞争性结合激酶的[[ATP结合口袋]]发挥作用，其独特的药理学特性使其在[[FLT3]]突变谱中具有广泛活性：<br />
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<li style="margin-bottom: 12px;"><strong>I型抑制剂特性：</strong>与只能结合非活性构象的II型抑制剂（如[[索拉非尼]]）不同，[[吉列替尼]]能同时结合[[FLT3]]激酶的[[活性构象]]和[[非活性构象]]。这使其能克服由[[D835]]等位点突变引起的[[TKD]]耐药。</li><br />
<li style="margin-bottom: 12px;"><strong>双重激酶抑制：</strong>通过抑制[[FLT3]]阻断下游[[PI3K/AKT]]、[[MAPK/ERK]]和[[STAT5]]信号通路。同时，抑制[[AXL]]激酶可逆转微环境介导的[[白血病细胞]]存活信号，从而应对白血病克隆的逃逸。</li><br />
<li style="margin-bottom: 12px;"><strong>诱导细胞凋亡：</strong>随着致癌驱动信号的中断，白血病原始细胞的[[增殖]]受到抑制，并迅速进入[[程序性死亡]]程序。</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;">临床图谱：ADMIRAL研究与生存获益</h2><br />
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<th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">评价维度</th><br />
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<th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">关键数据表现</th><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[总生存期]](OS)</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">R/R [[FLT3]]+ [[AML]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">[[吉列替尼]]组显著优于传统挽救性化疗（9.3个月 vs 5.6个月）。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[完全缓解率]](CR/CRh)</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">经治患者队列</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">达到约 34% 的复合完全缓解率，显著提升了后续[[造血干细胞移植]]的机会。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[安全性]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">长期服药人群</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">主要不良反应为[[肝酶]]升高、[[肌痛]]，以及特有的[[分化综合征]]风险。</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：分子筛查与围手术期管理</h2><br />
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[[吉列替尼]]的应用标志着[[AML]]进入靶向维持治疗新阶段：<br />
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<li style="margin-bottom: 12px;"><strong>强制分子检测：</strong>在诊断及复发时必须行[[NGS]]或[[PCR]]检测以确认[[FLT3]]突变状态。由于突变具有高度[[不稳定性]]，复发时的再次检测至关重要。</li><br />
<li style="margin-bottom: 12px;"><strong>[[分化综合征]]监测：</strong>少数患者会出现发热、呼吸困难等[[分化综合征]]表现，需通过[[地塞米松]]及时干预。</li><br />
<li style="margin-bottom: 12px;"><strong>移植桥接：</strong>对于复发患者，[[吉列替尼]]可作为一种高效的“[[桥接治疗]]”，帮助患者达到[[MRD]]阴性状态后再行[[异基因造血干细胞移植]]。</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>[[FLT3-ITD]]：</strong>内部串联重复，是[[AML]]中最常见的恶性预后指标。</li><br />
<li style="margin-bottom: 8px;"><strong>[[FLT3-TKD]]：</strong>点突变，常介导对早期[[FLT3抑制剂]]的抗药性。</li><br />
<li style="margin-bottom: 8px;"><strong>[[米朵妥林]] (Midostaurin)：</strong>首个获批用于[[AML]]一线的泛激酶抑制剂，通常与化疗联用。</li><br />
<li style="margin-bottom: 8px;"><strong>[[AXL激酶]]：</strong>一种生存信号激酶，其过表达常导致肿瘤对靶向药物的[[适应性耐药]]。</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>Perl AE, et al. (2019).</strong> <em>Gilteritinib or Chemotherapy for Relapsed or Refractory FLT3-Mutated AML.</em> <strong>[[The New England Journal of Medicine]]</strong>.[Academic Review]<br><br />
<span style="color: #475569;">[权威点评]：ADMIRAL研究奠定了吉列替尼在R/R AML中的标准地位，改写了全球诊疗指南。</span><br />
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[2] <strong>Daver NG, et al. (2022).</strong> <em>Targeting FLT3 mutations in AML: ongoing evolution of the therapeutic landscape.</em> <strong>[[Blood]]</strong>.<br><br />
<span style="color: #475569;">[核心价值]：深度解析了吉列替尼如何通过抑制AXL和FLT3双通路克服克隆演化带来的挑战。</span><br />
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[[吉列替尼]] ([[Gilteritinib]]) 诊疗生态 · 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;">关联靶点</td><br />
<td style="padding: 10px 15px; color: #334155;">[[FLT3]]•[[AXL]]•[[STAT5]]•[[ERK]]•[[MCL1]]</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;">代表药物</td><br />
<td style="padding: 10px 15px; color: #334155;">[[米朵妥林]]•[[奎扎替尼]] (Quizartinib)•[[索拉非尼]]•[[维奈克拉]]</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;">战略实体</td><br />
<td style="padding: 10px 15px; color: #334155;">[[Astellas Pharma]]•[[NMPA]]•[[FDA]]•[[MD Anderson Cancer Center]]</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;">研究前沿</td><br />
<td style="padding: 10px 15px; color: #334155;">[[吉列替尼用于移植后维持治疗]]•[[联合维奈克拉的无化疗方案]]•[[针对FLT3-F691L突变的下一代TKI]]</td><br />
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