查看“艾代拉利司”的源代码

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            <strong>[[艾代拉利司]]</strong>（<strong>[[Idelalisib]]</strong>，商品名：<strong>[[Zydelig]]</strong>）是全球首个获批上市的选择性小分子<strong>[[PI3Kδ]]</strong>（磷脂酰肌醇3-激酶δ亚型）抑制剂。该药物由<strong>[[吉利德科学]]</strong>（[[Gilead Sciences]]）研发，主要用于治疗<strong>[[慢性淋巴细胞白血病]]</strong>（[[CLL]]）、<strong>[[滤泡性淋巴瘤]]</strong>（[[FL]]）及<strong>[[小淋巴细胞淋巴瘤]]</strong>（[[SLL]]）。[[Idelalisib]]通过高度选择性地抑制在血液系统恶性肿瘤中过度表达的[[PI3Kδ]]亚型，阻断<strong>[[B细胞受体]]</strong>（[[BCR]]）下游信号通路，从而抑制恶性B细胞的增殖、存活及趋化能力。虽然其在二线治疗中具有显著疗效，但临床应用需严格监控其特有的免疫介导性不良反应。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[艾代拉利司]]</div>
            <div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[Idelalisib]] / [[Zydelig]] · 点击展开</div>
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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;">[[Idelalisib]]分子化学结构图</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[PI3Kδ]] / [[PIK3CD]]</div>
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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>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">5293([[PIK3CD]])</td>
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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>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[第一代PI3K抑制剂]]</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[CAS]]登记号</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">870281-82-6</td>
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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>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">415.42 Da</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药方式</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">口服 (150mg BID)</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">原研厂商</th>
                    <td style="padding: 12px; color: #0f172a;">[[吉利德科学]]</td>
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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：阻断B细胞存活中枢</h2>
    
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        [[艾代拉利司]]通过精准干预磷脂酰肌醇通路，切断恶性B细胞与其微环境的生存依赖：
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        <li style="margin-bottom: 12px;"><strong>同工酶特异性抑制：</strong>[[PI3K]]家族有多种亚型，其中[[PI3Kδ]]主要在白细胞中表达。[[艾代拉利司]]对δ亚型的选择性是其他亚型的数十倍，从而在保证强效抑瘤的同时减少了对葡萄糖代谢（α亚型相关）的影响。</li>
        <li style="margin-bottom: 12px;"><strong>阻断BCR信号通路：</strong>[[PI3Kδ]]是[[B细胞受体]]（[[BCR]]）信号的核心组件。[[艾代拉利司]]通过抑制[[PIP3]]的生成，阻止下游[[Akt]]及[[mTOR]]的活化，导致细胞周期停滞。</li>
        <li style="margin-bottom: 12px;"><strong>干扰趋化因子网：</strong>它能抑制[[CXCL12]]等趋化因子介导的归巢作用，促使恶性B细胞从受保护的淋巴结、骨髓微环境释放到外周循环，使其更容易受到化疗或抗体药物的打击。</li>
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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;">临床应用矩阵：Zydelig的研究图谱</h2>

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                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">适应症场景</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">联合方案</th>
                <th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">关键临床获益</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[复发/难治性CLL]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">+ [[利妥昔单抗]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">相较于单用利妥昔单抗，显著延长 [[PFS]]，死亡风险降低约80%。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[惰性B细胞淋巴瘤]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">单药治疗</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">针对双重难治（利妥昔单抗及烷化剂）患者，[[ORR]] 达到 57% 以上。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[SLL]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">后线挽救治疗</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">为无法耐受化疗的老年患者提供无化疗靶向选择。</td>
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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：毒性管理与安全性闭环</h2>
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        [[艾代拉利司]]的临床管理需严格关注其潜在的免疫相关性副作用，即“黑框警告”内容：
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        <li style="margin-bottom: 12px;"><strong>免疫介导性肠炎：</strong>患者可能出现严重的[[腹泻]]或[[结肠炎]]。临床需鉴别感染性与非感染性腹泻，必要时需使用[[糖皮质激素]]干预。</li>
        <li style="margin-bottom: 12px;"><strong>肝毒性监测：</strong>服药的前三个月必须定期监测[[转氨酶]]水平。一旦出现3级以上升高，必须停药直至恢复。</li>
        <li style="margin-bottom: 12px;"><strong>预防机会性感染：</strong>该药可导致[[中性粒细胞减少]]。治疗期间强制要求预防<strong>[[卡氏肺孢子菌肺炎]]</strong>（[[PJP]]）并定期监测<strong>[[巨细胞病毒]]</strong>（[[CMV]]）激活。</li>
        <li style="margin-bottom: 12px;"><strong>特殊毒性警示：</strong>需警惕[[非感染性肺炎]]及[[肠穿孔]]风险，此类并发症虽少见但具有致死性。</li>
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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>
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            <li style="margin-bottom: 8px;"><strong>[[PI3Kδ]]：</strong>主要表达于造血细胞的激酶，是B细胞恶性转化的关键枢纽。</li>
            <li style="margin-bottom: 8px;"><strong>[[伊布替尼]] (Ibrutinib)：</strong>常与艾代拉利司对比的 [[BTK]] 抑制剂，两者在 [[CLL]] 领域形成竞争。</li>
            <li style="margin-bottom: 8px;"><strong>[[Richter转化]]：</strong>[[CLL]]向高度侵袭性淋巴瘤转化的过程，艾代拉利司在此类高危患者中亦有探索。</li>
            <li style="margin-bottom: 8px;"><strong>[[杜韦利司]] (Duvelisib)：</strong>新一代PI3K δ/γ 双靶点抑制剂。</li>
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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>
        
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            [1] <strong>Furman RR, et al. (2014).</strong> <em>Idelalisib and rituximab in relapsed chronic lymphocytic leukemia.</em> <strong>[[The New England Journal of Medicine]]</strong>. 370:997-1007.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：该研究奠定了PI3K抑制剂在复发难治CLL治疗中的里程碑地位。</span>
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            [2] <strong>Gopal AK, et al. (2014).</strong> <em>PI3Kδ inhibition by idelalisib in patients with relapsed indolent lymphoma.</em> <strong>[[NEJM]]</strong>. 370:1008-1018.<br>
            <span style="color: #475569;">[核心价值]：首次在大样本研究中证实了针对惰性淋巴瘤的单药高效靶向策略。</span>
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            [[艾代拉利司]] (Idelalisib) 诊疗生态 · 知识图谱
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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;">关联因子</td>
                <td style="padding: 10px 15px; color: #334155;">[[Akt]]•[[mTOR]]•[[BTK]]•[[SYK]]•[[CD20]]•[[CXCR4]]</td>
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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/后继</td>
                <td style="padding: 10px 15px; color: #334155;">[[杜韦利司]]•[[库潘尼西]] (Copanlisib)•[[阿考替尼]]•[[维奈克拉]]</td>
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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>
                <td style="padding: 10px 15px; color: #334155;">[[吉利德科学]]•[[FDA]]•[[NMPA]]•[[ASH]]</td>
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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>
                <td style="padding: 10px 15px; color: #334155;">[[克服PI3K耐药机制研究]]•[[与BCL2抑制剂联合的无化疗方案]]•[[针对T细胞淋巴瘤的异病同治探索]]</td>
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