查看“Copanlisib”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>Copanlisib</strong>（研发代号：<strong>BAY 80-6946</strong>，商品名：<strong>Aliqopa</strong>）是一款高选择性、泛-I 类 <strong>PI3K 抑制剂</strong>，尤其对 <strong>PI3Kα</strong> 和 <strong>PI3Kδ</strong> 异构体表现出纳摩尔级的抑制活性。与同类药物不同，Copanlisib 采用<strong>[[静脉注射]]</strong>的给药方式，这种间歇性给药策略有助于降低其免疫相关副反应的发生率。临床上，它主要用于治疗既往接受过至少两次全身治疗的复发性<strong>[[滤泡性淋巴瘤]]</strong>（FL）。凭借其对 α 亚型的强力抑制，Copanlisib 在克服某些由代偿性信号激活引起的耐药方面具有独特优势，被认为是 B 细胞恶性肿瘤靶向治疗的重要工具。
        </p>
    </div>

    <div class="medical-infobox mw-collapsible" style="width: 100%; max-width: 320px; margin: 0 auto 35px auto; 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, #e0f2fe 0%, #bae6fd 100%); text-align: center; cursor: pointer;">
            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">Copanlisib</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Drug: Aliqopa (点击展开/折叠)</div>
        </div>
        
        <div class="mw-collapsible-content">
            <div style="padding: 25px; text-align: center; background-color: #f8fafc;">
                <div style="display: inline-block; background: #ffffff; border: 1px solid #e2e8f0; border-radius: 12px; padding: 20px; box-shadow: 0 4px 10px rgba(0,0,0,0.04);">
                    <div style="width: 150px; height: 100px; background-color: #f1f5f9; display: flex; align-items: center; justify-content: center; color: #94a3b8; font-size: 0.8em; border-radius: 8px;">Structure Placeholder</div>
                </div>
                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">PI3Kα/δ 双重抑制剂</div>
            </div>

            <table style="width: 100%; border-spacing: 0; border-collapse: collapse; font-size: 0.85em;">
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">通用名称</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">Copanlisib</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">关键靶点</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;">PI3Kα / PI3Kδ</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子式</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">C<sub>23</sub>H<sub>28</sub>N<sub>8</sub>O<sub>4</sub></td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">480.52 g/mol</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">CAS 登记号</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1032568-63-0</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药方式</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;"><strong>静脉滴注 (IV)</strong></td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">标准剂量</th>
                    <td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">60mg (D1, 8, 15)</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">周期设置</th>
                    <td style="padding: 6px 12px; color: #0f172a;">28天为一个周期</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：双重靶点的协同打击</h2>
    
    <p style="margin: 15px 0; text-align: justify;">
        Copanlisib 的独特性在于其对 PI3K 通路两个关键异构体的同步抑制，这为其提供了更广泛的抗肿瘤谱。
    </p>

    <ul style="padding-left: 25px; color: #334155;">
        <li style="margin-bottom: 12px;"><strong>抑制 PI3Kδ (p110δ)：</strong>
            <br>主要作用于造血细胞。通过阻断 BCR 信号传导，直接抑制 B 细胞恶性克隆的生存与增殖，并诱导<strong>[[促凋亡信号]]</strong>。</li>
        <li style="margin-bottom: 12px;"><strong>抑制 PI3Kα (p110α)：</strong>
            <br>PI3Kα 通常在许多实体瘤和淋巴瘤中表达。抑制 α 亚型不仅能直接对抗肿瘤，还能有效遏制由于 δ 抑制后可能出现的 α 亚型代偿性激活，从而减少耐药。</li>
        <li style="margin-bottom: 12px;"><strong>细胞因子调控：</strong>
            <br>Copanlisib 能够显著下调恶性 B 细胞内促生存趋化因子的表达，破坏肿瘤微环境中的保护性信号。</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;">临床图谱：基于 CHRONOS 研究</h2>
    
    <div style="background-color: #f0fdf4; border-left: 5px solid #22c55e; padding: 15px 20px; margin: 20px 0; border-radius: 4px;">
        <h3 style="margin-top: 0; color: #166534; font-size: 1.1em;">给药优势：间歇性 IV 给药</h3>
        <p style="margin-bottom: 0; text-align: justify; font-size: 0.95em; color: #334155;">
            与每日口服药物相比，Copanlisib 的每周一次间歇给药方式显著降低了慢性免疫介导性毒性（如严重结肠炎）的风险。但在给药后数小时内，患者可能会出现暂时性的<strong>[[一过性高血糖]]</strong>和<strong>[[一过性高血压]]</strong>。
        </p>
    </div>

    <div style="overflow-x: auto; margin: 30px auto; max-width: 95%;">
        <table style="width: 100%; border-collapse: collapse; border: 1.2px solid #cbd5e1; font-size: 0.95em; text-align: left;">
            <tr style="background-color: #f8fafc; border-bottom: 2px solid #0f172a;">
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">临床试验</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">设计与主要终点</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义</th>
            </tr>
            <tr>
                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[CHRONOS-1]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">单药治疗复发/难治性 FL。ORR 达到 59%，CR 达到 14%。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">获 FDA 加速批准用于三线 FL 治疗。</td>
            </tr>
            <tr>
                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[CHRONOS-3]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">联合利妥昔单抗。显著延长 PFS（21.5 vs 13.8 个月）。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">支持 Copanlisib 作为联合方案的基础。</td>
            </tr>
            <tr>
                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">CHRONOS-4</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">联合标准免疫化疗（如 BR 或 R-CHOP）。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">探索其在更前线治疗中的协同增效价值。</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;">治疗策略：代谢与感染的平衡</h2>
    <ul style="padding-left: 25px; color: #334155;">
        <li style="margin-bottom: 12px;"><strong>血糖监控：</strong> 由于抑制 PI3Kα 会干扰胰岛素信号，约 50% 的患者会出现输注后高血糖。通常为暂时性，但对糖尿病患者需严密监测。</li>
        <li style="margin-bottom: 12px;"><strong>血压管理：</strong> 输注当天可能出现急性血压升高，必要时需预防性给予降压药物。</li>
        <li style="margin-bottom: 12px;"><strong>感染预防：</strong> 需警惕中性粒细胞减少及机会性感染（如 PJP），治疗期间应常规监测血常规。</li>
    </ul>

    <div style="font-size: 0.92em; line-height: 1.6; color: #1e293b; margin-top: 50px; border-top: 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>Dreyling M, et al. (2017).</strong> <em>Phosphatidylinositol 3-Kinase Inhibition by Copanlisib in Relapsed or Refractory Indolent Lymphoma.</em> <strong>[[Journal of Clinical Oncology]]</strong>. 2017;35(19):2103-2112.<br>
            <span style="color: #475569;">[学术点评]：里程碑式的 CHRONOS-1 研究，首次大规模证实了 Copanlisib 在多种惰性淋巴瘤中的强效抗肿瘤活性。</span>
        </p>

        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [2] <strong>Matikas A, et al. (2018).</strong> <em>Copanlisib: A pan-class I PI3K inhibitor for the treatment of follicular lymphoma.</em> <strong>[[Expert Opinion on Pharmacotherapy]]</strong>. 2018;19(17):1949-1956.<br>
            <span style="color: #475569;">[学术点评]：系统评价。详细分析了 Copanlisib 的药代动力学优势及 IV 给药相对于口服给药的毒性优化。</span>
        </p>
        
        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [3] <strong>Dreyling M, et al. (2021).</strong> <em>Copanlisib plus rituximab versus placebo plus rituximab in patients with relapsed indolent non-Hodgkin lymphoma (CHRONOS-3).</em> <strong>[[The Lancet Oncology]]</strong>. 2021;22(5):678-689.<br>
            <span style="color: #475569;">[学术点评]：确证了联合免疫治疗方案能显著提高无进展生存期，为 FL 二线及以上治疗提供了重要循证依据。</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;">
            Copanlisib (Aliqopa) · 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;">药理机制</td>
                <td style="padding: 10px 15px; color: #334155;">[[泛-PI3K抑制剂]] • [[PI3Kα/δ 抑制]] • [[胰岛素抵抗]]</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;">关键疾病</td>
                <td style="padding: 10px 15px; color: #334155;">[[滤泡性淋巴瘤]] • [[边缘区淋巴瘤]] • [[惰性淋巴瘤]]</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;">对比药物</td>
                <td style="padding: 10px 15px; color: #334155;">[[Idelalisib]] (口服) • [[Duvelisib]] • [[Umbralisib]]</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;">特殊副作用</td>
                <td style="padding: 10px 15px; color: #334155;">[[输注后高血糖]] • [[暂时性高血压]] • [[免疫性肺炎]]</td>
            </tr>
        </table>
    </div>

</div>