查看“Panobinostat”的源代码

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            <strong>[[帕诺宾司他]]</strong>（<strong>[[Panobinostat]]</strong>，商品名：<strong>[[Farydak]]</strong>）是一种高效、口服的广谱<strong>[[组蛋白去乙酰化酶]]</strong>（<strong>[[HDAC]]</strong>）抑制剂，属于氧肟酸衍生物。作为一种强效的表观遗传调节药物，它能同时靶向I、II及IV型[[HDAC]]同工酶。通过抑制[[HDAC]]活性，[[帕诺宾司他]]诱导细胞内[[组蛋白]]及非组蛋白（如[[p53]]、[[HSP90]]、[[$\alpha$-tubulin]]）的高度乙酰化，进而导致染色质重塑、细胞周期停滞并诱导<strong>[[凋亡]]</strong>。在2026年的临床体系中，该药主要联合[[硼替佐米]]和[[地塞米松]]，用于治疗复发或难治性<strong>[[多发性骨髓瘤]]</strong>（[[RRMM]]），是表观遗传治疗药物在血液恶性肿瘤领域的代表性分子。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[帕诺宾司他]]</div>
            <div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[Panobinostat]] / [[Farydak]] · 点击展开</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[HDAC1]]/[[2]]/[[3]]/[[6]]</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%;">[[CAS]]登记号</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">404950-80-7</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;">[[广谱HDAC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;">[[Entrez]]ID</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">3065 / 3066 / 8841</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子式</th>
                    <td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">$C_{21}H_{23}N_{3}O_{2}$</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;">349.43 Da</td>
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                    <th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">开发公司</th>
                    <td style="padding: 12px; color: #0f172a;">[[诺华]] / [[SecuraBio]]</td>
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        [[帕诺宾司他]]的作用机制通过纠正肿瘤细胞内异常的乙酰化水平来发挥抗癌活性：
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        <li style="margin-bottom: 12px;"><strong>染色质重塑：</strong>通过抑制[[HDAC1]]、[[HDAC2]]和[[HDAC3]]，[[帕诺宾司他]]增加组蛋白末端[[赖氨酸]]残基的乙酰化，使致密的染色质结构变得松散（[[常染色质]]化），从而重新激活被沉默的抑癌基因。</li>
        <li style="margin-bottom: 12px;"><strong>干扰HSP90伴侣功能：</strong>抑制[[HDAC6]]可诱导<strong>[[HSP90]]</strong>高度乙酰化，削弱其对致癌客户蛋白（如[[BCR-ABL]]、[[FLT3]]、[[Akt]]）的稳定作用，加速这些癌蛋白的泛素化降解。</li>
        <li style="margin-bottom: 12px;"><strong>蛋白质组应激：</strong>在骨髓瘤细胞中，[[帕诺宾司他]]与[[蛋白酶体抑制剂]]（如[[硼替佐米]]）产生强协同作用。通过抑制[[HDAC6]]介导的[[聚集体]]（[[Aggresome]]）途径，导致错误折叠蛋白蓄积，诱发致命的[[内质网应激]]。</li>
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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;">核心临床数据 (Panorama 1)</th>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[复发难治骨髓瘤]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">+ [[硼替佐米]] + [[地塞米松]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">相比标准方案，显著延长中位 [[PFS]]（12个月 vs 8个月）。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[既往二线治疗失败]]</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">三联方案</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">针对经[[来那度胺]]治疗后的亚群表现出更显著的获益优势。</td>
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                <td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">安全性考量</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1;">(黑框警告内容)</td>
                <td style="padding: 8px; border: 1px solid #cbd5e1; color: #e11d48;">需严格监控严重[[腹泻]]及致命性[[心律失常]]（[[QT间期延长]]）。</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：风险管理与个体化剂量</h2>
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        2026年精准医疗共识强调了[[帕诺宾司他]]应用中的“效毒平衡”策略：
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        <li style="margin-bottom: 12px;"><strong>序贯给药优化：</strong>推荐采用间歇给药方案（如每周三次，每三周停一周），以缓解胃肠道毒性。</li>
        <li style="margin-bottom: 12px;"><strong>心脏安全性筛查：</strong>治疗前必须评估 [[ECG]] 及血清电解质（尤其是[[钾]]、[[镁]]）。对于 [[QTc]] > 450ms 的患者应避免使用。</li>
        <li style="margin-bottom: 12px;"><strong>耐药逆转策略：</strong>当患者对[[蛋白酶体抑制剂]]产生获得性耐药时，加入[[帕诺宾司他]]可显著提高肿瘤细胞对[[硼替佐米]]的二次敏感度。</li>
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            <li style="margin-bottom: 8px;"><strong>[[HDAC]]：</strong>负责去除乙酰基，使组蛋白与 DNA 结合紧密，抑制基因转录。</li>
            <li style="margin-bottom: 8px;"><strong>[[表观遗传学]]治疗：</strong>不改变 DNA 序列，通过调节基因表达水平来对抗肿瘤。</li>
            <li style="margin-bottom: 8px;"><strong>[[伏立诺他]] (Vorinostat)：</strong>首个获批的 HDAC 抑制剂，但帕诺宾司他的效价（[[IC50]]）通常更高。</li>
            <li style="margin-bottom: 8px;"><strong>[[HSP90]]：</strong>一种分子伴侣，其功能受乙酰化状态严格调控。</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>San-Miguel JF, et al. (2014).</strong> <em>Panobinostat plus bortezomib and dexamethasone versus placebo plus bortezomib and dexamethasone in patients with relapsed or relapsed and refractory multiple myeloma (PANORAMA 1).</em> <strong>[[The Lancet Oncology]]</strong>. 15(11):1195-206.[Academic Review]<br>
            <span style="color: #475569;">[权威点评]：该项关键 III 期研究奠定了帕诺宾司他在骨髓瘤三联方案中的核心地位。</span>
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            [2] <strong>Laubach JP, et al. (2015).</strong> <em>Panobinostat for the treatment of multiple myeloma.</em> <strong>[[Expert Opinion on Investigational Drugs]]</strong>.<br>
            <span style="color: #475569;">[核心价值]：系统阐述了 HDAC 抑制剂在协同蛋白酶体通路中的分子药理逻辑。</span>
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            [[帕诺宾司他]] (Panobinostat) 药效生态 · 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;">[[HDAC1]]•[[HDAC6]]•[[HSP90]]•[[p53]]•[[p21]]•[[Aggresome]]</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;">联合/迭代</td>
                <td style="padding: 10px 15px; color: #334155;">[[硼替佐米]]•[[卡非佐米]]•[[达雷妥尤单抗]]•[[西达本胺]]</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;">[[Novartis]]•[[SecuraBio]]•[[FDA]]•[[NCCN]]</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;">前沿方向</td>
                <td style="padding: 10px 15px; color: #334155;">[[克服蛋白酶体抑制剂耐药]]•[[针对三阴性乳腺癌的联合探索]]•[[选择性HDAC6抑制剂研发]]</td>
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