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<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>[[埃佐万替尼]]</strong>（<strong>[[Elzovantinib]]</strong>，研发代码：<strong>[[TPX-0022]]</strong>）是一种创新的、高选择性的口服多靶点<strong>[[酪氨酸激酶抑制剂]]</strong>（[[TKI]]）。该药物最初由[[Turning Point Therapeutics]]（现属[[百时美施贵宝]]/[[BMS]]）研发，采用独特的[[大环]]结构设计，旨在同时靶向<strong>[[MET]]</strong>（[[肝细胞生长因子受体]]）、<strong>[[CSF1R]]</strong>（[[集落刺激因子1受体]]）和<strong>[[SRC]]</strong>激酶。[[埃佐万替尼]]不仅能直接抑制由[[MET]]变异驱动的肿瘤细胞生长，还能通过调节肿瘤微环境（抑制[[肿瘤相关巨噬细胞]]）和封锁[[SRC]]介导的耐药旁路，实现对[[非小细胞肺癌]]及[[胃癌]]等实体瘤的协同打击。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[埃佐万替尼]]</div><br />
<div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[Elzovantinib]] / [[TPX-0022]] · 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;">[[TPX-0022]]大环分子构象模型</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">主要靶点：[[MET]] / [[CSF1R]] / [[SRC]]</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: 40%;">[[Entrez]]ID</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">4233 / 1436</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 / 2433</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 / P07333</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;">[[小分子激酶抑制剂]]</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;">约477.5Da</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">持有公司</th><br />
<td style="padding: 12px; color: #0f172a;">[[百时美施贵宝]](BMS)</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：三位一体的协同打击</h2><br />
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[[埃佐万替尼]]的独特性在于其超越了传统的单一[[MET抑制剂]]，通过精准干预三个关键信号轴来克服肿瘤耐药：<br />
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<li style="margin-bottom: 12px;"><strong>MET激酶抑制：</strong>通过紧凑的大环结构结合在[[MET]]受体的[[ATP]]结合口袋，阻断[[HGF]]诱导的信号传导。这对于携带<strong>[[MET 14外显子跳变]]</strong>或<strong>[[MET扩增]]</strong>的肿瘤具有直接的致死作用。</li><br />
<li style="margin-bottom: 12px;"><strong>CSF1R介导的微环境重塑：</strong>通过抑制[[CSF1R]]，[[埃佐万替尼]]能减少肿瘤组织中[[M2型]][[肿瘤相关巨噬细胞]]（[[TAMs]]）的浸润。这种免疫微环境的改善可解除对[[T细胞]]的抑制，增强整体抗肿瘤免疫。</li><br />
<li style="margin-bottom: 12px;"><strong>SRC信号阻断：</strong>[[SRC]]家族激酶是许多靶向治疗产生[[获得性耐药]]的旁路核心。[[埃佐万替尼]]对[[SRC]]的抑制能有效预防或逆转由[[SRC]]激活介导的[[MET-TKI]]耐药。</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;">核心临床研究矩阵</h2><br />
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<th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">研究名称</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">研究人群/适应症</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">当前临床价值与获益</th><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[SHIELD-1]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">[[MET]]变异晚期实体瘤</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">I/II期研究显示，在携带[[MET 14跳变]]的[[NSCLC]]及[[胃癌]]中展现了令人鼓舞的[[ORR]]。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[联用方案探索]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">联合[[免疫检查点抑制剂]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">利用其调节微环境的特性，正探索与[[PD-1单抗]]联用以提升应答深度。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[脑转移研究]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">伴[[脑转移]]的[[NSCLC]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">早期数据显示该分子具有一定的[[血脑屏障]]穿透潜力。</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：精准识别与安全性管理</h2><br />
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作为新一代多靶点[[TKI]]，[[埃佐万替尼]]的应用遵循高度个体化的管理原则：<br />
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<li style="margin-bottom: 12px;"><strong>[[分子标志物]]驱动：</strong>在使用前必须通过[[NGS]]检测确认是否存在<strong>[[MET 14外显子跳变]]</strong>、<strong>[[MET扩增]]</strong>或[[MET]]融合。这些基因型是预测获益的核心指标。</li><br />
<li style="margin-bottom: 12px;"><strong>[[安全性]]概况：</strong>常见的不良反应包括[[转氨酶升高]]、[[外周水肿]]及[[胃肠道毒性]]。由于其抑制[[CSF1R]]，需关注对[[免疫系统]]和[[血液系统]]的潜在影响。</li><br />
<li style="margin-bottom: 12px;"><strong>[[耐药后处理]]：</strong>若出现病情进展，建议行二次[[活检]]或[[液体活检]]，以识别可能的[[激酶域]]点突变（如[[D1228]]、[[Y1230]]等）并调整后续方案。</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>[[MET 14外显子跳变]]：</strong>肺癌中的一种强驱动变异，是[[埃佐万替尼]]的首要打击靶标。</li><br />
<li style="margin-bottom: 8px;"><strong>[[CSF1R]]：</strong>调节巨噬细胞生存的关键受体，其抑制与肿瘤[[免疫微环境]]改善直接相关。</li><br />
<li style="margin-bottom: 8px;"><strong>[[大环结构设计]]：</strong>通过刚性化分子构象提高亲和力并减少脱靶风险的[[药物化学]]策略。</li><br />
<li style="margin-bottom: 8px;"><strong>[[百时美施贵宝]]：</strong>该药物目前的全球商业权利持有方。</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>Cho BC, et al. (2021).</strong> <em>SHIELD-1: A Phase 1/2 Study of TPX-0022, a MET/CSF1R/SRC Inhibitor, in Patients with Advanced Solid Tumors.</em> <strong>[[AACR]] Annual Meeting Abstract</strong>.[Academic Review]<br><br />
<span style="color: #475569;">[权威点评]：该研究初步证实了埃佐万替尼在多靶点抑制及安全性方面的平衡优势。</span><br />
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[2] <strong>Turning Point Therapeutics Research Team. (2022).</strong> <em>Macrocyclic MET inhibitor TPX-0022 potently inhibits MET, CSF1R, and SRC and induces tumor regression.</em> <strong>[[The Journal of Hematology & Oncology]]</strong>.<br><br />
<span style="color: #475569;">[核心价值]：系统解析了三靶点抑制在大环架构下的药理优势。</span><br />
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[[埃佐万替尼]] ([[TPX-0022]]) 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]]•[[CSF1R]]•[[SRC]]•[[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;">竞争/同类</td><br />
<td style="padding: 10px 15px; color: #334155;">[[赛沃替尼]] (Savolitinib)•[[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;">[[百时美施贵宝]]•[[FDA]]•[[NMPA]]</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;">[[克服MET获得性突变研究]]•[[针对辅助治疗领域的剂量优化]]•[[与新型免疫激动剂的联合应用]]</td><br />
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223.160.136.36