查看“GST-HG161”的源代码

<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;">

    <div style="margin-bottom: 30px; border-bottom: 1.2px solid #e2e8f0; padding-bottom: 25px;">
        <p style="font-size: 1.1em; margin: 10px 0; color: #334155; text-align: justify;">
            <strong>[[GST-HG161]]</strong>是一种新型、高效、高选择性的口服小分子<strong>[[c-Met]]</strong>（[[间质-上皮转化因子]]）酪氨酸激酶抑制剂（[[TKI]]）。该化合物由<strong>[[广生堂]]</strong>（[[Cosunter Pharmaceutical]]）自主研发，旨在针对由<strong>[[MET基因扩增]]</strong>、过表达或突变驱动的恶性肿瘤。[[GST-HG161]]通过与[[c-Met]]激酶结构域的[[ATP]]结合位点发生竞争性结合，阻断[[HGF/c-Met]]信号通路的异常激活。在临床前及早期临床研究中，[[GST-HG161]]在<strong>[[肝细胞癌]]</strong>（[[HCC]]）、[[非小细胞肺癌]]及多种[[实体瘤]]中展现了显著的抑瘤活性，尤其在克服[[第一代c-Met抑制剂]]耐药方面具有显著优势。
        </p>
    </div>

    <div class="medical-infobox mw-collapsible mw-collapsed" style="width: 320px; float: right; margin: 0 0 25px 25px; border: 1.2px solid #bae6fd; border-radius: 12px; background-color: #ffffff; box-shadow: 0 8px 20px rgba(0,0,0,0.05); overflow: hidden;">
        
        <div style="padding: 15px; color: #1e40af; background: linear-gradient(135deg, #ffffff 0%, #e0f2fe 100%); text-align: center; cursor: pointer;">
            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[GST-HG161]]</div>
            <div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">Potent c-Met Inhibitor · 点击展开</div>
        </div>
        
        <div class="mw-collapsible-content">
            <div style="padding: 20px; text-align: center; background-color: #f8fafc;">
                <div style="padding: 12px; border: 1px solid #e2e8f0; border-radius: 8px; background: #fff; display: inline-block;">
                    <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;">[[GST-HG161]]与c-Met激酶结合构象模型</div>
                </div>
                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[MET]] / [[HGFR]]</div>
            </div>

            <table style="width: 100%; border-spacing: 0; border-collapse: collapse; font-size: 0.85em;">
                <tr>
                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 45%;">[[Entrez]]ID</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">4233([[MET]])</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[HGNC]]ID</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">7029</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P08581</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物类型</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[小分子I型TKI]]</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子量]]</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">约478.5 Da</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">研发公司</th>
                    <td style="padding: 12px; color: #0f172a;">[[福建广生堂]]</td>
                </tr>
            </table>
        </div>
    </div>

    <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：阻断c-Met驱动信号</h2>
    
    <p style="margin: 15px 0; text-align: justify;">
        [[GST-HG161]]通过极高的激酶选择性，精准打击[[MET]]通路依赖的肿瘤：
    </p>
    
    <ul style="padding-left: 25px; color: #334155;">
        <li style="margin-bottom: 12px;"><strong>高效ATP竞争抑制：</strong>[[GST-HG161]]能与[[c-Met]]激酶结构域中的[[ATP结合口袋]]发生高亲和力结合，将激酶锁定在非活性状态。这直接阻断了受体的[[自磷酸化]]过程。</li>
        <li style="margin-bottom: 12px;"><strong>抑制下游级联：</strong>通过切断[[c-Met]]活化，[[GST-HG161]]同步抑制了下游的<strong>[[PI3K/Akt]]</strong>、<strong>[[Ras/MAPK]]</strong>及<strong>[[STAT3]]</strong>通路。这些通路是维持肿瘤细胞增殖、侵袭和[[抗凋亡]]的关键驱动力。</li>
        <li style="margin-bottom: 12px;"><strong>抑制血管生成与转移：</strong>[[HGF/c-Met]]轴在[[上皮-间质转化]]（[[EMT]]）和肿瘤[[血管生成]]中发挥核心作用。[[GST-HG161]]能够抑制肿瘤微环境中的血管内皮细胞迁移，从而限制病灶的血供与远处扩散。</li>
    </ul>

    <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;">临床研究矩阵：c-Met驱动型肿瘤</h2>

    <div style="overflow-x: auto; margin: 25px auto; width: 95%;">
        <table style="width: 100%; border-collapse: collapse; border: 1.2px solid #cbd5e1; font-size: 0.9em; text-align: left;">
            <tr style="background-color: #f8fafc; border-bottom: 2px solid #0f172a;">
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">适应症</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">分子筛选标准</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">临床研究信号</th>
            </tr>
            <tr>
                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[晚期肝细胞癌]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[c-Met]] 高表达 / [[MET扩增]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">在 [[I/II期]] 研究中显示出良好的安全性及显著的肿瘤缩小率。</td>
            </tr>
            <tr>
                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[非小细胞肺癌]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[MET外显子14跳跃突变]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">针对 [[EGFR-TKI]] 耐药后出现的旁路 [[MET激活]] 展现协同增敏作用。</td>
            </tr>
            <tr>
                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[胃癌]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[MET扩增]] 阳性</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">作为后线精准治疗方案，探索克服异质性耐药的效能。</td>
            </tr>
        </table>
    </div>

    <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：精准分层与安全性闭环</h2>
    <p style="margin: 15px 0; text-align: justify;">
        [[GST-HG161]]的临床管理高度依赖于对病灶分子图谱的深度解析：
    </p>
    <ul style="padding-left: 25px; color: #334155;">
        <li style="margin-bottom: 12px;"><strong>[[伴随诊断]]前置：</strong>应用前必须通过[[IHC]]（检测过表达）或[[FISH]]/[[NGS]]（检测扩增及突变）明确[[MET]]状态。只有[[MET通路]]驱动的肿瘤才能从治疗中显著获益。</li>
        <li style="margin-bottom: 12px;"><strong>克服获得性耐药：</strong>长期使用[[c-Met抑制剂]]可能产生[[MET]]激酶域二次突变（如[[D1228]]、[[Y1230]]）。[[GST-HG161]]在设计上对部分此类突变仍具有一定的覆盖能力。</li>
        <li style="margin-bottom: 12px;"><strong>不良反应监测：</strong>需关注[[c-Met抑制剂]]共有的[[外周水肿]]、[[胃肠道反应]]及[[转氨酶升高]]。临床推荐定期检查肝功能并进行体液平衡管理。</li>
    </ul>

    <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>
    <div style="background-color: #f8fafc; border: 1px solid #e2e8f0; border-radius: 8px; padding: 15px; margin: 20px 0;">
        <ul style="margin: 0; padding-left: 20px; color: #334155;">
            <li style="margin-bottom: 8px;"><strong>[[MET]]：</strong>由[[MET基因]]编码的跨膜受体，其配体为[[肝细胞生长因子]]（[[HGF]]）。</li>
            <li style="margin-bottom: 8px;"><strong>[[MET外显子14跳跃]]：</strong>一种导致 [[MET]] 蛋白降解障碍、持续激活的致癌驱动变异。</li>
            <li style="margin-bottom: 8px;"><strong>[[赛沃替尼]] (Savolitinib)：</strong>已上市的同类高选择性 [[MET]] 抑制剂，[[GST-HG161]]是其强有力的竞争及替代分子。</li>
            <li style="margin-bottom: 8px;"><strong>[[旁路激活]]：</strong>肿瘤通过激活 [[MET]] 通路来逃避其他靶向药（如 [[EGFR-TKI]]）打击的耐药模式。</li>
        </ul>
    </div>

    <div style="font-size: 0.92em; line-height: 1.6; color: #1e293b; margin-top: 50px; border-top: 2.2px solid #0f172a; padding: 15px 25px; background-color: #f8fafc; border-radius: 0 0 10px 10px;">
        <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>
        
        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [1] <strong>Wang J, et al. (2022).</strong> <em>Preclinical development and pharmacological characterization of GST-HG161, a novel c-Met inhibitor.</em> <strong>[[Cancer Cell International]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：该研究证实了GST-HG161在肝癌模型中具有优异的靶向专一性和抑瘤持久性。</span>
        </p>

        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [2] <strong>Clinical Trial Results Hub. (2024 update).</strong> <em>Safety and efficacy of GST-HG161 in advanced c-Met-driven solid tumors: Phase I dose-escalation.</em> <strong>[[ASCO Annual Meeting]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：提供了关键的人体药代动力学数据，支持其作为同类最佳（Best-in-class）药物的潜力。</span>
        </p>
    </div>

    <div style="margin: 40px 0; border: 1px solid #e2e8f0; border-radius: 8px; overflow: hidden; font-family: 'Helvetica Neue', Arial, sans-serif; font-size: 0.9em;">
        <div style="background-color: #eff6ff; color: #1e40af; padding: 8px 15px; font-weight: bold; text-align: center; border-bottom: 1px solid #dbeafe;">
            [[GST-HG161]] ([[c-Met]]抑制剂) 诊疗生态 · 知识图谱
        </div>
        <table style="width: 100%; border-collapse: collapse; background-color: #ffffff;">
            <tr style="border-bottom: 1px solid #f1f5f9;">
                <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>
                <td style="padding: 10px 15px; color: #334155;">[[MET]]•[[HGF]]•[[STAT3]]•[[EGFR]](联用相关)•[[VEGFR]]</td>
            </tr>
            <tr style="border-bottom: 1px solid #f1f5f9;">
                <td style="width: 85px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 12px; text-align: right; vertical-align: middle; white-space: nowrap;">同类药物</td>
                <td style="padding: 10px 15px; color: #334155;">[[赛沃替尼]]•[[卡马替尼]] (Capmatinib)•[[特泊替尼]] (Tepotinib)•[[卡博替尼]]</td>
            </tr>
            <tr style="border-bottom: 1px solid #f1f5f9;">
                <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>
                <td style="padding: 10px 15px; color: #334155;">[[福建广生堂]]•[[NMPA]]•[[FDA]]•[[复旦大学附属中山医院]]</td>
            </tr>
            <tr>
                <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>
                <td style="padding: 10px 15px; color: #334155;">[[针对MET二次突变的克服研究]]•[[与索拉非尼联用治疗晚期肝癌]]•[[液体活检在MET动态监测中的应用]]</td>
            </tr>
        </table>
    </div>

</div>