查看“夫拉平度”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>[[夫拉平度]]</strong>（<strong>[[Flavopiridol]]</strong>，又名<strong>[[阿伏西地]]</strong>/<strong>[[Alvocidib]]</strong>）是全球首个进入临床试验的<strong>[[多靶点细胞周期蛋白依赖性激酶]]</strong>（[[CDK]]）抑制剂。作为一种源自植物生物碱[[Rohitukine]]的半合成黄酮类化合物，它能强效竞争性结合[[CDK1]]、[[CDK2]]、[[CDK4]]、[[CDK6]]以及<strong>[[CDK9]]</strong>的[[ATP]]结合口袋。在2026年的血液肿瘤治疗体系中，[[夫拉平度]]主要通过抑制[[CDK9]]干扰<strong>[[P-TEFb]]</strong>复合物，进而下调[[MCL-1]]等抗凋亡蛋白的转录，在<strong>[[急性髓系白血病]]</strong>（[[AML]]）及<strong>[[慢性淋巴细胞白血病]]</strong>（[[CLL]]）的联合化疗方案中展现出独特的诱导凋亡价值。
        </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;">[[夫拉平度]]</div>
            <div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[Flavopiridol]] / [[Alvocidib]] · 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>
                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[CDK9]] / [[Pan-CDK]]</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;">1022([[CDK9]])</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[CAS]]号</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">146426-40-6</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;">[[小分子激酶抑制剂]]</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;">401.8 Da</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药途径</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">静脉注射 (IV)</td>
                </tr>
                <tr>
                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">开发公司</th>
                    <td style="padding: 12px; color: #0f172a;">[[Tolero Pharmaceuticals]]</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：双重拦截与转录切断</h2>
    
    <p style="margin: 15px 0; text-align: justify;">
        [[夫拉平度]]具有双重抗肿瘤机制，不仅能够锁定细胞周期，更能从根源阻断抗凋亡信号：
    </p>
    
    <ul style="padding-left: 25px; color: #334155;">
        <li style="margin-bottom: 12px;"><strong>细胞周期阻滞（Pan-CDK抑制）：</strong> 通过抑制[[CDK1]]、[[CDK2]]和[[CDK4/6]]，[[夫拉平度]]能将癌细胞拦截在[[G1/S]]期和[[G2/M]]期交界处，直接抑制肿瘤细胞增殖。</li>
        <li style="margin-bottom: 12px;"><strong>转录抑制（CDK9核心效应）：</strong> [[CDK9]]是[[正转录延伸因子b]]（[[P-TEFb]]）的核心组分。[[夫拉平度]]抑制[[CDK9]]后，阻止了[[RNA聚合酶II]]的[[C-末端结构域]]（[[CTD]]）磷酸化。</li>
        <li style="margin-bottom: 12px;"><strong>快速下调[[MCL-1]]：</strong> 由于[[MCL-1]]蛋白的[[mRNA]]半衰期极短，转录受阻会导致[[MCL-1]]水平迅速下降，使肿瘤细胞对凋亡信号极端敏感，从而克服耐药。</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;">核心临床研究矩阵</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%;">试验名称/代号</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">联合方案/适应症</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">2026年临床结论</th>
            </tr>
            <tr>
                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[ZELLA-101]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">+ [[阿糖胞苷]] + [[柔红霉素]] (AML)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">在[[MCL-1]]高表达的[[初治白血病]]中显示显著的[[CR]]率。</td>
            </tr>
            <tr>
                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[CheckMate方案]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">序贯[[Venetoclax]] (CLL)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">[[夫拉平度]]预处理可有效克服由[[MCL-1]]介导的[[BCL-2]]抑制剂耐药。</td>
            </tr>
            <tr>
                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[实体瘤探索]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">单药/联合 (肉瘤)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">作为[[广谱CDK]]抑制剂，在部分[[细胞周期蛋白变异]]的肉瘤中观察到疾病稳定。</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：风险分层与毒性闭环</h2>
    <p style="margin: 15px 0; text-align: justify;">
        [[夫拉平度]]的临床应用由于其强效的诱导凋亡能力，需高度关注安全性管理：
    </p>
    <ul style="padding-left: 25px; color: #334155;">
        <li style="margin-bottom: 12px;"><strong>[[肿瘤溶解综合征]]（[[TLS]]）防控：</strong> [[夫拉平度]]引起的肿瘤细胞大规模死亡极易诱发致命的[[TLS]]。临床需严格进行水化、[[碱化]]及[[别嘌醇]]预处理。</li>
        <li style="margin-bottom: 12px;"><strong>给药剂量逻辑：</strong> 现代方案倾向于采用“[[推注-输注]]”（[[Bolus-Infusion]]）模式，以确保在短时间内达到抑制[[CDK9]]所需的血药浓度峰值。</li>
        <li style="margin-bottom: 12px;"><strong>针对[[MCL-1]]依赖人群：</strong> 通过[[BH3谱图]]（[[BH3 Profiling]]）检测肿瘤对[[MCL-1]]的依赖程度，是筛选[[夫拉平度]]获益人群的最佳策略。</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>[[CDK9]]：</strong> 转录调节的核心激酶，是[[夫拉平度]]发挥抗白血病作用的最主要靶标。</li>
            <li style="margin-bottom: 8px;"><strong>[[MCL-1]]：</strong> 关键抗凋亡蛋白，其水平的快速波动决定了肿瘤细胞对治疗的应答。</li>
            <li style="margin-bottom: 8px;"><strong>[[P-TEFb]]复合物：</strong> 包含[[CDK9]]和[[Cyclin T]]，负责启动mRNA的延伸阶段。</li>
            <li style="margin-bottom: 8px;"><strong>[[Venetoclax]]：</strong> [[BCL-2]]抑制剂，常与[[夫拉平度]]形成协同治疗方案。</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>Zeidner JF, et al. (2015/2026 update).</strong> <em>Alvocidib (flavopiridol) followed by 7+3 chemotherapy in newly diagnosed AML patients with poor-risk genetics.</em> <strong>[[Blood]]</strong>.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：该项研究奠定了夫拉平度作为转录启动调节剂在AML序贯治疗中的先驱地位。</span>
        </p>

        <p style="margin: 12px 0; border-bottom: 1px solid #e2e8f0; padding-bottom: 10px;">
            [2] <strong>Karp JE, et al. (2011).</strong> <em>Sequential flavopiridol, cytosine arabinoside, and mitoxantrone: a phase II trial in adults with poor-risk AML.</em> <strong>[[Clinical Cancer Research]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：提供了夫拉平度在难治性白血病中克服多重耐药的早期生化证据。</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;">
            [[夫拉平度]] ([[Alvocidib]]) 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;">[[CDK9]]•[[CDK1]]•[[CDK4]]•[[MCL-1]]•[[BCL-2]]</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;">竞争/伙伴</td>
                <td style="padding: 10px 15px; color: #334155;">[[Dinaciclib]]•[[Venetoclax]]•[[阿糖胞苷]]</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;">[[Tolero Pharmaceuticals]]•[[NCI]]•[[FDA]]</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MYC驱动肿瘤的转录抑制研究]]•[[新型选择性CDK9抑制剂开发]]•[[克服白血病耐药的组合疗法]]</td>
            </tr>
        </table>
    </div>

</div>