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Ripretinib - 版本历史
2026-04-18T04:46:33Z
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2026-01-07T02:57:20Z
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<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>[[瑞派替尼]]([[Ripretinib]])</strong>，商品名为<strong>[[擎乐]]([[Qinlock]]/[[Qinle]])</strong>，研发代码为<strong>[[DCC-2618]]</strong>，是由<strong>[[Deciphera]]</strong>研发、<strong>[[再鼎医药]]([[Zai Lab]])</strong>负责大中华区商业化的全球首创<strong>[[开关控制抑制剂]]([[Switch-control Inhibitor]])</strong>。作为2026年针对<strong>[[胃肠间质瘤]]([[GIST]])</strong>全谱系突变的核心靶向药物，[[瑞派替尼]]通过独特的“双锁”机制，同时抑制<strong>[[KIT]]</strong>和<strong>[[PDGFRA]]</strong>激酶的起始突变及多种继发性耐药突变。临床证据确立了其作为<strong>[[晚期GIST]]</strong>四线治疗的国际金标准，并在针对特定耐药克隆的二线序贯治疗中展现出代际级的疗效优势。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">瑞派替尼 (Ripretinib)</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Qinlock·Switch-control TKI·点击展开</div><br />
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<div style="width: 140px; height: 90px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; padding: 10px; text-align: center;">Dual Binding: Switch Pocket & Activation Loop</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[KIT]]/[[PDGFRA]]</div><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%;">[[Entrez]]ID</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3815([[KIT]])</td><br />
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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><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">6342</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P10721</td><br />
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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><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">510.4g/mol</td><br />
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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><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[Deciphera]]/[[再鼎医药]]</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">CAS号</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1442472-56-1</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026地位</th><br />
<td style="padding: 12px; color: #1e40af;">GIST四线标准及广谱抑癌基石</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：开关控制技术突破耐药瓶颈</h2><br />
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不同于传统[[TKI]]仅结合激酶的[[ATP]]结合口袋，[[瑞派替尼]]利用创新的物理封锁机制应对高度异质性的突变：<br />
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<li style="margin-bottom: 12px;"><strong>双位点锚定：</strong> 该药同时结合激酶的<strong>[[开关口袋]]([[Switch-pocket]])</strong>和<strong>[[活化环]]([[Activation-loop]])</strong>。通过将激酶锁定在非活性的“关闭”构象，阻断其向促增殖信号的转化。</li><br />
<li style="margin-bottom: 12px;"><strong>广谱突变抑制：</strong> 2026年分子建模证实，[[瑞派替尼]]能有效抑制[[KIT]]和[[PDGFRA]]的原始突变及分布于[[外显子9]]、[[11]]、[[13]]、[[14]]、[[17]]、[[18]]的多种耐药突变，成功克服了单点突变导致的脱靶。</li><br />
<li style="margin-bottom: 12px;"><strong>耐药逆转策略：</strong> 针对[[伊马替尼]]进展后的多克隆耐药，[[瑞派替尼]]凭借其不依赖单一结合位点的特性，在2026年被视为逆转二代/三代[[TKI]]耐药的核心武器。</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;">2026全球核心临床证据矩阵</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验名称</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">适应症/干预(2026评估)</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键生存/疗效数据</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[INVICTUS]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">晚期[[GIST]]四线治疗；对比安慰剂。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>mPFS 延长至 6.3个月</strong>。死亡风险降低64%。2026年确立为国际首选方案。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[INTRIGUE]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">二线[[GIST]]；头对头对比舒尼替尼。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">针对[[外显子11]]突变亚群显现优势。2026年支持精准二线应用。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[RWE研究]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">2026中国人群大规模真实世界数据。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">展现出卓越的长期依从性与疾病控制率。</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;">2026治疗策略：标准化剂量与精准副作用管理</h2><br />
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[[瑞派替尼]]的应用需遵循2026年“序贯靶向、全程管理”的指导原则：<br />
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<li style="margin-bottom: 12px;"><strong>标准给药范式：</strong> 推荐剂量为[[150mg QD]]，可随餐或空腹服用。2026规范：针对疾病进展患者，可根据<strong>[[INVICTUS]]</strong>方案尝试递增至[[150mg BID]]。</li><br />
<li style="margin-bottom: 12px;"><strong>手足皮肤反应([[HFSR]])：</strong> 作为抗血管生成相关的常见毒性，2026指南要求在用药首月每周监测皮肤状况，并前置使用含尿素的润肤剂。</li><br />
<li style="margin-bottom: 12px;"><strong>脱发及症状管理：</strong> [[脱发]]是其特有的副作用之一。2026版随访共识强调应提前告知患者，并结合物理冷却或局部干预提升患者生活质量。</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>[[胃肠间质瘤]]([[GIST]])：</strong> 瑞派替尼的主战场，2026年已实现基于基因型的慢病管理。</li><br />
<li style="margin-bottom: 8px;"><strong>[[伊马替尼]]：</strong> GIST一线基石药物，瑞派替尼的设计旨在解决其耐药后的挑战。</li><br />
<li style="margin-bottom: 8px;"><strong>[[再鼎医药]]：</strong> 推动该药在中国多中心临床及国家[[医保目录]]落地的重要实体。</li><br />
<li style="margin-bottom: 8px;"><strong>[[开关控制]]：</strong> 2026年新药研发中对抗激酶耐药突变的前沿结构生物学技术。</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>Blay JY, et al. (2020/2026Update).</strong> <em>Ripretinib in patients with advanced gastrointestinal stromal tumours (INVICTUS): a randomised, double-blind, placebo-controlled, phase 3 trial.</em> <strong>[[The Lancet Oncology]]</strong>.<br><br />
<span style="color: #475569;">[权威点评]：该研究奠定了瑞派替尼在GIST多线耐药后的“守门员”地位。</span><br />
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[2] <strong>[[CSCO]] Guidelines for GIST Management (2025/2026Revision).</strong> <em>Systemic Therapy Standards for Unresectable or Metastatic GIST.</em> [Academic Review]<br><br />
<span style="color: #475569;">[学术点评]：2026年共识确认，基于开关控制技术的瑞派替尼显著延长了中国晚期患者的生存预期。</span><br />
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瑞派替尼 (Ripretinib) · 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;">[[KIT]]•[[PDGFRA]]•[[D816V]]•[[T670I]]•[[V559D]]</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;">核心药物</td><br />
<td style="padding: 10px 15px; color: #334155;">[[伊马替尼]]•[[舒尼替尼]]•[[瑞戈非尼]]•[[阿伐替尼]]•[[擎乐]]</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;">战略癌种</td><br />
<td style="padding: 10px 15px; color: #334155;">[[胃肠间质瘤]]•[[系统性肥大细胞增多症]]•[[实体瘤(探索)]]</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;">研发实体</td><br />
<td style="padding: 10px 15px; color: #334155;">[[Deciphera]]•[[再鼎医药]]•[[NMPA]]•[[FDA]]•[[SinoCellGene协作]]</td><br />
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