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莫普替尼 - 版本历史
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<p><b>新页面</b></p><div><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;"><br />
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<strong>[[莫普替尼]]([[Momelotinib]])**，商品名为**[[Ojjaara]]**，研发代码为**[[GS-0387]]**或**[[CYT387]]</strong>，是由[[葛兰素史克]]([[GSK]])开发的一种强效、口服的<strong>[[Janus激酶]]([[JAK]])</strong>抑制剂。与其他[[JAK2抑制剂]]不同，[[莫普替尼]]具有独特的<strong>[[ACVR1]]</strong>（[[ALK2]]）抑制活性。临床上，该药物被批准用于治疗患有中危或高危<strong>[[骨髓纤维化]]</strong>（包括原发性及继发性）且伴有<strong>[[贫血]]</strong>的成人患者。其核心价值在于，在有效回缩脾脏和改善全身症状的同时，能够显著降低铁调素水平，促进红细胞生成，从而改善或消除患者对输血的依赖。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">莫普替尼 (Momelotinib)</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Ojjaara·JAK1/JAK2/ACVR1抑制剂·点击展开</div><br />
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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;">Momelotinib Structure: ATP-competitive inhibitor of JAK/ACVR1</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心特性：改善贫血</div><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">[[CAS]]号</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">1056634-68-4</td><br />
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<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">25127112</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">分子量</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">414.5g/mol</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">主要靶点</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">JAK1 / JAK2 / ACVR1</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药剂量</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">200mg 每日一次</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">研发厂家</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">[[GSK]] (原Sierra)</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">核心标签</th><br />
<td style="padding: 12px; color: #b91c1c;">贫血型骨髓纤维化首选</td><br />
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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;">药理机制：双重靶向实现“增效减毒”</h2><br />
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[[莫普替尼]]的独特性在于其对三种核心激酶的选择性抑制，通过协同效应解决了传统治疗带来的骨髓抑制难题：<br />
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<li style="margin-bottom: 12px;"><strong>JAK1/JAK2 阻断：</strong> 通过抑制 [[JAK1]] 和 [[JAK2]] 磷酸化，切断过度活跃的信号瀑布，从而抑制恶性髓系克隆增殖，缓解<strong>[[脾脏肿大]]</strong>及因促炎细胞因子（如 [[IL-6]]）升高导致的全身乏力、盗汗等症状。</li><br />
<li style="margin-bottom: 12px;"><strong>ACVR1 轴干预：</strong> [[ACVR1]]（激活素A受体1型）负责诱导肝脏产生<strong>[[铁调素]]</strong>（Hepcidin）。莫普替尼抑制 [[ACVR1]] 可导致铁调素水平下降，解除其对铁转运蛋白的抑制，恢复铁利用和<strong>[[促红细胞生成素]]</strong>响应，从根本上改善贫血。</li><br />
<li style="margin-bottom: 12px;"><strong>解决输血依赖：</strong> 与[[芦可替尼]]可能诱发或加重贫血不同，莫普替尼在治疗过程中往往能提升血红蛋白水平，使部分原本依赖输血的患者实现<strong>[[脱离输血]]</strong>。</li><br />
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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;">核心临床获益矩阵</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">试验名称</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">人群背景</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">关键客观获益与评价</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[MOMENTUM]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">曾用过 JAKi 且伴有贫血的 MF 患者；对比[[达那唑]]。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">在症状缓解、脾脏缩小及<strong>[[输血独立率]]</strong>方面均显著优于对照组。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[SIMPLIFY-1]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">一线未经治疗的 MF 患者；对比[[芦可替尼]]。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">脾脏回缩获益非劣效，但莫普替尼组的贫血改善指标显著更优。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[SIMPLIFY-2]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">二线或后线治疗；对比最佳现有疗法（BAT）。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">证明了其在多种前期方案进展后的挽救价值。</td><br />
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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：基于血细胞计数的精准分流</h2><br />
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[[莫普替尼]]的临床应用策略强调“**[[纠正贫血与控制疾病并重]]**”：<br />
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<li style="margin-bottom: 12px;"><strong>贫血型患者的首选：</strong> 临床指南建议，对于基线血红蛋白 < 10g/dL 或存在输血依赖的 MF 患者，莫普替尼应作为一线或早期序贯的优先选择。</li><br />
<li style="margin-bottom: 12px;"><strong>剂量维持优势：</strong> 相比于其他抑制剂因贫血常需减量或停药，莫普替尼通常能维持 <strong>200mg QD</strong> 的全剂量给药，确保了对脾脏肿大的持续抑制压力。</li><br />
<li style="margin-bottom: 12px;"><strong>安全性监测：</strong> 需关注常见的腹泻及潜在的周围神经病变。治疗过程中应动态监测血小板计数，虽其贫血耐受性好，但仍需警惕严重的骨髓抑制风险。</li><br />
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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><br />
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<li style="margin-bottom: 8px;"><strong>[[铁调素]]([[Hepcidin]])：</strong> 调节体内铁平衡的核心蛋白，其异常升高是骨髓纤维化贫血的主因。</li><br />
<li style="margin-bottom: 8px;"><strong>[[ACVR1]]/[[ALK2]]：</strong> 莫普替尼的特色靶点，通过干预该通路实现促红细胞生成作用。</li><br />
<li style="margin-bottom: 8px;"><strong>[[输血独立]]：</strong> 衡量莫普替尼疗效的关键临床指标，指连续 12周以上无需输红细胞。</li><br />
<li style="margin-bottom: 8px;"><strong>[[芦可替尼]]耐药：</strong> 指使用一线 JAKi 后疗效不佳，莫普替尼是此类患者的重要序贯药物。</li><br />
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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><br />
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[1] <strong>Verstovsek S, et al. (2023).</strong> <em>Momelotinib versus danazol in symptomatic patients with myelofibrosis and anaemia (MOMENTUM): a double-blind, randomised, phase 3 study.</em> <strong>[[The Lancet]]</strong>.<br><br />
<span style="color: #475569;">[权威点评]：该项研究奠定了莫普替尼在贫血型骨髓纤维化患者中的标准治疗地位，确立了 ACVR1 抑制的临床收益。</span><br />
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[2] <strong>Gerds AT, et al. (2023Update).</strong> <em>Phase III Trials of Momelotinib in Myelofibrosis: Integrated Analysis of Simplify and Momentum.</em> <strong>[[Journal of Clinical Oncology]]</strong>.[Academic Review]<br><br />
<span style="color: #475569;">[学术点评]：综述全面论证了莫普替尼在改善骨髓纤维化整体疾病负荷的同时，对贫血症状的独特逆转作用。</span><br />
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莫普替尼 (Momelotinib) 诊疗生态 · 知识图谱<br />
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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;">关联靶点</td><br />
<td style="padding: 10px 15px; color: #334155;">[[JAK1]]•[[JAK2]]•[[ACVR1]]•[[STAT3]]•[[STAT5]]•[[铁调素]]</td><br />
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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;">核心药物</td><br />
<td style="padding: 10px 15px; color: #334155;">[[芦可替尼]]•[[非达替尼]]•[[帕克替尼]]•[[达那唑]]•[[地舒单抗]]</td><br />
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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><br />
<td style="padding: 10px 15px; color: #334155;">[[GSK]]•[[Sierra Oncology]]•[[SinoCellGene协作]]•[[FDA]]•[[NMPA]]</td><br />
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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;">前沿驱动</td><br />
<td style="padding: 10px 15px; color: #334155;">[[铁代谢重塑研究]]•[[与BCL-2抑制剂联合]]•[[早期干预延缓纤维化]]•[[CAR-NK序贯策略]]</td><br />
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