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Qinle - 版本历史
2026-04-19T09:12:03Z
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2026-01-07T02:42:09Z
<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>[[瑞派替尼]]([[Ripretinib]])</strong>，商品名为<strong>[[擎乐]]([[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>在大中华区商业化的全球首个<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>全谱系突变的核心药物，[[瑞派替尼]]通过独特的双重作用机制，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。在2026年的临床指南中，它不仅是<strong>[[晚期GIST]]</strong>四线及后线治疗的全球金标准，并在针对特定耐药克隆的二线治疗及<strong>[[系统性肥大细胞增多症]]</strong>领域展现了卓越的临床价值。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">瑞派替尼 (擎乐)</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Ripretinib (Qinle)·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;">Ripretinib Binding to KIT Switch Pocket and Activation Loop</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心机制：[[开关控制]]抑制</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/商业化</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;">给药剂量</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">150mg QD (口服)</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全谱系耐药解决方案</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：开关控制技术与广谱突变抑制</h2><br />
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[[瑞派替尼]]的设计逻辑打破了传统[[TKI]]仅结合单一激酶构象的局限，2026年的分子药理学解析如下：<br />
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<li style="margin-bottom: 12px;"><strong>双位点锚定：</strong> 该药物同时结合激酶的<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，阻止受体自磷酸化及下游信号传导。</li><br />
<li style="margin-bottom: 12px;"><strong>克服KIT多位点耐药：</strong> 不同于[[索拉非尼]]或[[瑞戈非尼]]对特定外显子突变的局限，[[瑞派替尼]]能有效抑制包括[[外显子9]]、[[11]]、[[13]]、[[14]]、[[17]]及[[18]]在内的多种继发性突变，特别是针对[[D816V]]等难治性突变表现出更优活性。</li><br />
<li style="margin-bottom: 12px;"><strong>受体泛性抑制：</strong> 对<strong>[[PDGFRA]]</strong>激酶（包括罕见的[[D842V]]突变，虽非首选但具活性）同样具备抑制效能，为复杂分型的[[GIST]]提供了多维封锁。</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/人群(2026评价)</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键生存/获益数据</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;">四线及以后晚期[[GIST]]；多中心III期。</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%。奠定四线金标准。</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年确立分层二线地位。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[真实世界研究]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">2026中国人群大规模数据汇总。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[DCR]]达80%以上。展现出优于前代TKI的长期依从性。</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：精准计量与症状管理</h2><br />
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[[瑞派替尼]]在2026年的临床路径强调“获益最大化与毒性最小化”：<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年临床共识建议：针对耐药进展患者，可考虑在严密监测下通过<strong>[[剂量递增]]</strong>（至150mg BID）尝试克服二次耐药。</li><br />
<li style="margin-bottom: 12px;"><strong>皮肤及毛发毒性监测：</strong> 核心关注<strong>[[脱发]]</strong>、<strong>[[手足皮肤反应]]</strong>（[[HFSR]]）及高血压。2026规范要求：首月每周随访，脱发患者需前置心理干预，HFSR建议配合尿素霜局部预防。</li><br />
<li style="margin-bottom: 12px;"><strong>伴随诊断的价值：</strong> 虽然瑞派替尼具有广谱性，但2026年策略仍提倡通过<strong>[[cfDNA]]液体活检</strong>监测突变谱演变，以精细化调整治疗时机。</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> 消化道最常见的间叶源性肿瘤，[[KIT]]/[[PDGFRA]]突变为主要驱动。</li><br />
<li style="margin-bottom: 8px;"><strong>[[再鼎医药]]：</strong> 擎乐在中国市场的推广主体，推动了其进入国家[[医保目录]]。</li><br />
<li style="margin-bottom: 8px;"><strong>[[开关控制抑制剂]]：</strong> 2026年抗耐药药物研发的重要技术分支。</li><br />
<li style="margin-bottom: 8px;"><strong>[[伊马替尼]]：</strong> GIST一线治疗的奠基药物，其耐药后产生的异质性突变为瑞派替尼的作用背景。</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 double-blind, randomised, placebo-controlled, phase 3 trial.</em> <strong>[[The Lancet Oncology]]</strong>.<br><br />
<span style="color: #475569;">[权威点评]：该研究确立了瑞派替尼在GIST后线治疗中不可动摇的霸主地位，通过开关控制技术打破了耐药僵局。</span><br />
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[2] <strong>[[CSCO]] Guidelines for GIST Management (2025/2026Revision).</strong> <em>Integrating Ripretinib into the Precision Treatment Algorithm for Advanced GIST.</em> [Academic Review]<br><br />
<span style="color: #475569;">[学术点评]：2026年共识确认，[[瑞派替尼]]在中国人群中展现了优异的可及性与获益比。</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]]•[[V560G]]•[[T670I]]</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;">[[擎乐]]•[[伊马替尼]]•[[舒尼替尼]]•[[瑞戈非尼]]•[[阿伐替尼]]</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;">治疗病种</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;">研究机构</td><br />
<td style="padding: 10px 15px; color: #334155;">[[Deciphera]]•[[再鼎医药]]•[[SinoCellGene协作]]•[[FDA]]</td><br />
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223.160.138.166