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Glumetinib - 版本历史
2026-04-18T20:38:25Z
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2026-01-16T05:50:59Z
<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>[[谷美替尼]]</strong>（<strong>[[Glumetinib]]</strong>，商品名：<strong>[[海益坦]]</strong>）是一种强效、高选择性、口服的小分子<strong>[[c-Met]]</strong>（[[间质-上皮转化因子]]）酪氨酸激酶抑制剂（[[TKI]]）。该药物由<strong>[[海和药物]]</strong>（[[Haihe Biopharma]]）自主研发，旨在精准打击由<strong>[[MET外显子14跳跃突变]]</strong>（[[METex14 skipping]]）驱动的恶性肿瘤。[[谷美替尼]]通过与[[c-Met]]激酶结构域的[[ATP]]结合位点竞争性结合，有效阻断[[HGF/c-Met]]信号通路的异常激活。临床数据显示，[[谷美替尼]]具有起效快、脑渗透率高以及安全性良好的特点，是针对[[MET]]驱动型<strong>[[非小细胞肺癌]]</strong>（[[NSCLC]]）的一线及后线精准治疗的重要利器。<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;">[[Glumetinib]] / [[海益坦]] · 点击展开</div><br />
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<div style="padding: 12px; border: 1px solid #e2e8f0; border-radius: 8px; background: #fff; display: inline-block;"><br />
<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;">[[Glumetinib]]与c-Met蛋白结合模型</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]] / [[HGFR]]</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;">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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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P08581</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;">[[高选择性Ib型TKI]]</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;">473.5 Da</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">主要适应症</th><br />
<td style="padding: 12px; color: #0f172a;">[[METex14跳变NSCLC]]</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：垂直封锁c-Met信号通路</h2><br />
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[[谷美替尼]]通过高特异性的激酶结合模式，精准阻断肿瘤细胞的生长动力：<br />
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<li style="margin-bottom: 12px;"><strong>ATP竞争性抑制：</strong>[[谷美替尼]]属于[[I型c-Met抑制剂]]，能以高亲和力结合在[[c-Met]]激酶催化结构域的[[ATP]]口袋。通过阻止[[ATP]]的结合，药物抑制了[[c-Met]]受体的[[自磷酸化]]。</li><br />
<li style="margin-bottom: 12px;"><strong>拦截METex14跳变信号：</strong>[[MET外显子14跳跃突变]]会导致[[c-Met]]蛋白泛素化降解受阻，使蛋白持续处于活化状态。[[谷美替尼]]能直接针对这种过度积累的活化蛋白进行强效抑制。</li><br />
<li style="margin-bottom: 12px;"><strong>血脑屏障高穿透性：</strong>该分子具有优异的理化性质，能够高效跨越[[血脑屏障]]（[[BBB]]）。这对于治疗合并[[脑转移]]的肺癌患者至关重要，可在脑脊液中维持有效的抑瘤浓度。</li><br />
<li style="margin-bottom: 12px;"><strong>多通路阻断：</strong>通过阻断[[c-Met]]活化，同步抑制下游的[[PI3K/Akt]]、[[MAPK/ERK]]及[[STAT3]]等促进细胞生存与迁移的关键通路。</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;">临床评价矩阵：GLORY研究与前沿进展</h2><br />
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<th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">研究项目/人群</th><br />
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<th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">临床疗效信号([[ORR]]/[[PFS]])</th><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[初治NSCLC]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">[[METex14 skipping]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">客观缓解率([[ORR]])达到 60% 以上，展现极高的一线治疗价值。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[经治NSCLC]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">[[METex14 skipping]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">针对化疗或[[免疫治疗]]进展患者，仍能获得 40%-50% 的应答率。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[肺癌脑转移]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">颅内病灶</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">颅内客观缓解率([[iORR]])表现优异，显著延长中位缓解持续时间。</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：精准识别与安全性闭环</h2><br />
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[[谷美替尼]]的临床应用基于个体化分子检测与全过程毒性监测：<br />
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<li style="margin-bottom: 12px;"><strong>伴随诊断前置：</strong>推荐通过[[NGS]]（[[二代测序]]）或[[RT-PCR]]对患者进行[[MET外显子14跳变]]检测。不推荐仅根据[[IHC]]高表达作为单药使用依据。</li><br />
<li style="margin-bottom: 12px;"><strong>管理外周水肿：</strong>[[水肿]]是[[MET抑制剂]]常见的副反应。建议临床监测体重及血清白蛋白水平，必要时使用[[利尿剂]]或调整剂量。</li><br />
<li style="margin-bottom: 12px;"><strong>克服旁路耐药：</strong>对于出现[[MET抑制剂]]耐药的患者，需通过[[液体活检]]监测是否出现[[MET激酶域二次突变]]（如[[D1228]]、[[Y1230]]）或[[EGFR]]旁路激活。</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>[[METex14跳跃突变]]：</strong>导致[[c-Met]]蛋白降解结构域缺失，引起细胞持续增殖的驱动基因变异。</li><br />
<li style="margin-bottom: 8px;"><strong>[[赛沃替尼]] (Savolitinib)：</strong>另一款国产高选择性[[MET抑制剂]]，与[[谷美替尼]]形成竞争互补。</li><br />
<li style="margin-bottom: 8px;"><strong>[[Capmatinib]] / [[Tepotinib]]：</strong>全球范围内已获批的同类高选择性[[MET-TKI]]。</li><br />
<li style="margin-bottom: 8px;"><strong>[[c-Met]]：</strong>受体酪氨酸激酶，是多种实体瘤发生发展及耐药的关键驱动因子。</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>Glumetinib (SCC244) in patients with non-small cell lung cancer harboring MET exon 14 skipping: results from the Phase II GLORY trial.</em> <strong>[[The Lancet Respiratory Medicine]]</strong>.[Academic Review]<br><br />
<span style="color: #475569;">[权威点评]：GLORY研究证实了谷美替尼在METex14跳变人群中的强效抗肿瘤活性及显著的安全性。</span><br />
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[2] <strong>NCCN Guidelines. (2026 update).</strong> <em>Non-Small Cell Lung Cancer: Targeted Therapy for MET exon 14 skipping mutations.</em> <strong>[[NCCN]]</strong>.<br><br />
<span style="color: #475569;">[核心价值]：确立了高选择性MET抑制剂在MET驱动型肺癌临床管理中的基石地位。</span><br />
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[[谷美替尼]] (Glumetinib) 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]](旁路激活)•[[Akt]]•[[ERK]]</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;">竞品/类似</td><br />
<td style="padding: 10px 15px; color: #334155;">[[赛沃替尼]]•[[卡马替尼]]•[[特泊替尼]]•[[伯瑞替尼]]</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;">战略实体</td><br />
<td style="padding: 10px 15px; color: #334155;">[[海和药物]]•[[中国科学院上海药物研究所]]•[[NMPA]]•[[CSCO]]</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;">[[联合EGFR-TKI攻克耐药]]•[[针对MET扩增的精准化分级]]•[[围手术期新辅助治疗探索]]</td><br />
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223.160.138.164