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2026-04-19T02:42:57Z
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2026-01-16T02:29:15Z
<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>[[谷美替尼]]</strong>（<strong>[[Vebreltinib]]</strong>，商品名：<strong>[[海益坦]]</strong>）是一种强效、高选择性的口服<strong>[[MET]]</strong>激酶抑制剂。作为一种[[小分子]]酪氨酸激酶抑制剂（[[TKI]]），它主要通过竞争性结合[[MET]]蛋白的[[ATP]]结合口袋，阻断由[[肝细胞生长因子]]（[[HGF]]）诱导的信号传导。[[谷美替尼]]在临床上被批准用于治疗携带<strong>[[MET14外显子跳变]]</strong>（[[METex14 skipping]]）的局部晚期或转移性<strong>[[非小细胞肺癌]]</strong>（[[NSCLC]]）。其出色的药代动力学特性、显著的颅内活性以及良好的安全性，使其成为[[MET]]改变驱动型肺癌精准治疗的重要手段。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[谷美替尼]]</div><br />
<div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[Vebreltinib]] / [[SCC-244]] · 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;">[[MET]]激酶受体结合示意</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[MET]] (c-Met)</div><br />
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<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">4233([[MET]])</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;">7029</td><br />
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<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Q04912</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[CAS]]登记号</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1655514-64-5</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;">512.51Da</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">研发厂商</th><br />
<td style="padding: 12px; color: #0f172a;">[[海和药物]]</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：精准靶向MET异常信号</h2><br />
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[[谷美替尼]]作为一种高选择性的[[TKI]]，主要通过干扰[[MET]]受体酪氨酸激酶的催化功能来抑制肿瘤生长：<br />
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<li style="margin-bottom: 12px;"><strong>竞争性结合：</strong>[[谷美替尼]]特异性地结合在[[MET]]激酶结构域的[[ATP]]口袋中。通过物理占据该位点，它防止了[[ATP]]的结合，从而阻止了激酶的[[自磷酸化]]。</li><br />
<li style="margin-bottom: 12px;"><strong>阻断信号级联：</strong>受体失活直接切断了下游的<strong>[[RAS/MAPK]]</strong>、<strong>[[PI3K/AKT]]</strong>和<strong>[[STAT]]</strong>等关键信号通路。这些通路被认为是驱动细胞[[增殖]]、[[存活]]和[[侵袭]]的核心引擎。</li><br />
<li style="margin-bottom: 12px;"><strong>攻克14外显子跳变：</strong>[[MET14外显子]]编码[[近膜结构域]]，含有介导[[c-Cbl]]结合并导致受体降解的序列。当发生跳变时，[[MET]]蛋白无法被正常降解，导致受体在细胞表面大量积累。[[谷美替尼]]能够有效抑制这种持续性的癌信号。</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：GLORY研究与核心获益</h2><br />
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<th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">评价指标</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">研究队列人群</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">临床数据表现</th><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[客观缓解率]](ORR)</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">初治 [[METex14]] 突变患者</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">展现出极高的应答水平（部分研究报道超过60%）。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[颅内ORR]](iORR)</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">伴有[[脑转移]]的患者亚组</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">证实了优异的[[血脑屏障]]穿透力，颅内病灶缩小显著。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[缓解持续时间]](DoR)</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">全体入组患者</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">中位应答持久，反映了深度的表观调控和肿瘤抑制。</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：精准分层与副作用管理</h2><br />
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[[谷美替尼]]的临床应用需遵循高度精准化的流程，以确保疗效最大化：<br />
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<li style="margin-bottom: 12px;"><strong>基因检测前置：</strong>在使用前必须通过[[NGS]]（[[二代测序]]）或[[RT-PCR]]确认<strong>[[MET14外显子跳变]]</strong>状态。对于[[MET扩增]]的患者，临床研究亦显示出潜在的获益空间。</li><br />
<li style="margin-bottom: 12px;"><strong>副作用监控：</strong>常见不良反应包括[[外周水肿]]、[[谷丙转氨酶]]（[[ALT]]）/[[谷草转氨酶]]（[[AST]]）升高。临床需定期监测肝功能及肾功能指标。</li><br />
<li style="margin-bottom: 12px;"><strong>耐药路径探索：</strong>若发生进展，应考虑检测是否出现[[MET]]激酶域的[[二次突变]]（如[[D1228]]、[[Y1230]]）或其它旁路激活（如[[EGFR扩增]]）。</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>[[MET14外显子跳变]]：</strong>一种驱动致癌变异，导致[[MET]]受体泛素化失效和降解受阻。</li><br />
<li style="margin-bottom: 8px;"><strong>[[赛沃替尼]] (Savolitinib)：</strong>另一种国产高选择性 [[MET-TKI]]，常作为对比研究的对象。</li><br />
<li style="margin-bottom: 8px;"><strong>[[血脑屏障]] (BBB)：</strong>[[谷美替尼]]在设计中优化的特性，确保其在[[中枢神经系统]]的治疗浓度。</li><br />
<li style="margin-bottom: 8px;"><strong>[[HGF]]：</strong>[[MET]]受体的天然配体，其异常上调常介导肿瘤的耐药。</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>Lu S, et al. (2023).</strong> <em>Vebreltinib (SCC-244) in patients with advanced NSCLC harboring MET exon 14 skipping mutations (GLORY): a multicenter, open-label, phase II study.</em> <strong>[[The Lancet Respiratory Medicine]]</strong>.[Academic Review]<br><br />
<span style="color: #475569;">[权威点评]：GLORY研究确立了谷美替尼在中国人群中的高效应答及良好的安全性特征。</span><br />
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[2] <strong>Zhang T, et al. (2022).</strong> <em>Discovery and preclinical characterization of Vebreltinib, a potent and selective MET inhibitor.</em> <strong>[[Molecular Cancer Therapeutics]]</strong>.<br><br />
<span style="color: #475569;">[核心价值]：解析了SCC-244的分子发现过程及其针对各种MET变异的抑制谱。</span><br />
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[[谷美替尼]] ([[Vebreltinib]]) 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;">[[MET]]•[[HGF]]•[[EGFR]]•[[RAS]]•[[AKT]]</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;">[[赛沃替尼]]•[[卡马替尼]] (Capmatinib)•[[特泊替尼]] (Tepotinib)</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;">[[海和药物]]•[[NMPA]]•[[CSCO]]•[[上海胸科医院]]</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;">[[针对MET扩增的联合用药研究]]•[[克服MET获得性耐药的小分子研发]]•[[谷美替尼用于其它实体瘤的探索]]</td><br />
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