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Ciforadenant - 版本历史
2026-04-18T13:39:24Z
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2026-01-06T05:43:59Z
<p>建立内容为“<div style="padding: 0 4%; line-height: 1.8; color: #1e293b; font-family: 'Helvetica Neue', Helvetica, 'PingFang SC', Arial, sans-serif; background-color: #ffffff…”的新页面</p>
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<strong>[[西福拉腺苷]]([[Ciforadenant]])</strong>，研发代码为<strong>[[CPI-444]]</strong>，是一种在研的、强效且具有高度选择性的口服小分子<strong>[[腺苷A2a受体]]([[A2aR]])</strong>拮抗剂。该药物由<strong>[[CorvusPharmaceuticals]]</strong>开发。在2026年的肿瘤免疫治疗体系中，[[Ciforadenant]]被定位为克服肿瘤微环境([[TME]])中腺苷介导免疫抑制的关键药物。通过竞争性封锁T细胞和NK细胞表面的[[A2aR]]，[[Ciforadenant]]旨在通过重启被“耗竭”的免疫细胞，增强<strong>[[PD-1]]</strong>或<strong>[[CTLA-4]]</strong>抑制剂的疗效。临床研究正重点探索其在<strong>[[肾细胞癌]]([[RCC]])</strong>及其他晚期实体瘤中的联合治疗潜力。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">西福拉腺苷</div><br />
<div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px; white-space: nowrap;">Ciforadenant (CPI-444)·点击展开</div><br />
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阿 <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);"><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[A2aR]]</div><br />
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<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">135([[ADORA2A]])</td><br />
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<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P29274</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;">约411.4Da</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">药物类型</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">小分子受体拮抗剂</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药频率</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">每日一次或两次(口服)</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">研发阶段</th><br />
<td style="padding: 6px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">临床I/II期(2026)</td><br />
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<th style="text-align: left; padding: 6px 12px; background-color: #f1f5f9; color: #475569;">2026状态</th><br />
<td style="padding: 12px; color: #1e40af;">腺苷通路联合开发热点</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;">分子机制：阻断腺苷抑制信号</h2><br />
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肿瘤微环境中的高水平<strong>[[腺苷]]</strong>（由于[[CD39]]和[[CD73]]介导的[[ATP]]降解产生）是导致免疫逃逸的核心因素之一。[[Ciforadenant]]的作用机制聚焦于：<br />
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<li style="margin-bottom: 12px;"><strong>拮抗 A2aR 信号传导：</strong><br />
腺苷结合[[A2a]]受体会激活[[腺苷酸环化酶]]，增加[[T细胞]]内的[[cAMP]]浓度，从而抑制[[细胞因子]]分泌。[[Ciforadenant]]通过占据结合位点，防止这一抑制级联反应的发生。</li><br />
<li style="margin-bottom: 12px;"><strong>免疫细胞功能重启：</strong><br />
通过阻断[[A2aR]]，该药能恢复<strong>[[CD8+效应T细胞]]</strong>的增殖能力和<strong>[[NK细胞]]</strong>的杀伤活性。2026年的前沿研究揭示，其能显著下调肿瘤微环境中的<strong>[[调节性T细胞]]([[Tregs]])</strong>比例。</li><br />
<li style="margin-bottom: 12px;"><strong>协同增敏效应：</strong><br />
最新的转录组学数据显示，[[Ciforadenant]]能上调肿瘤细胞表面<strong>[[MHC-I]]</strong>类分子的表达，使其更易被经[[PD-1]]抑制剂激活的免疫系统识别。</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;">2026临床研究与产出图谱</h2><br />
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<th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">疾病场景</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">2026联合方案(在研)</th><br />
<th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">临床意义</th><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">难治性[[RCC]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">[[Ciforadenant]]联合<strong>[[阿替利珠单抗]]</strong>。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>针对PD-1耐药患者</strong>。探索二线及以后的挽救方案。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">晚期实体瘤</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">联合[[CD73]]抑制剂。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;"><strong>双腺苷通路阻断</strong>。从生成和接收两端封锁腺苷轴。</td><br />
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<td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[B细胞淋巴瘤]]</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">单药及联合化免方案探索。</td><br />
<td style="padding: 10px; border: 1px solid #cbd5e1;">2026年II期扩展数据显示出部分病理缓解潜力。</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;">2026治疗策略：生物标志物导向的联合</h2><br />
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[[Ciforadenant]]在2026年的开发策略高度依赖于精准的微环境表型分析：<br />
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<li style="margin-bottom: 12px;"><strong>腺苷特征评分(Adenosine Signature)：</strong> 2026年临床共识建议，通过测定肿瘤组织中<strong>[[A2aR]]</strong>和<strong>[[CD73]]</strong>的mRNA表达负荷，来预测患者对[[Ciforadenant]]的响应率。</li><br />
<li style="margin-bottom: 12px;"><strong>口服管理优势：</strong> 作为小分子口服药物，其便利性使其成为免疫联合方案中理想的“辅助调节剂”，可与静脉注射的[[PD-1]]药物形成差异化用药节奏。</li><br />
<li style="margin-bottom: 12px;"><strong>安全性分层：</strong> 重点关注潜在的<strong>[[中枢神经系统]]</strong>及心血管副作用（如失眠、心悸）。2026规范推荐，剂量滴定需参考个体的[[cAMP]]抑制动力学。</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>[[腺苷通路]]：</strong> 目前免疫肿瘤学中仅次于PD-1/CTLA-4的热点抑制性通路。</li><br />
<li style="margin-bottom: 8px;"><strong>[[CD73]]：</strong> 腺苷生成的关键酶，与[[A2aR]]共同构成腺苷信号轴。</li><br />
<li style="margin-bottom: 8px;"><strong>[[Etrumadenant]]：</strong> 竞争对手开发的A2aR/A2bR双重拮抗剂，常与[[Ciforadenant]]对比药效。</li><br />
<li style="margin-bottom: 8px;"><strong>[[免疫冷肿瘤]]：</strong> [[Ciforadenant]]旨在通过腺苷阻断将其转变为“热肿瘤”。</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>Fong L,et al.(2020/2025Update).</strong> <em>Adenosine 2A Receptor Blockade as a Strategy to Overcome Resistance to Anti-PD-1/PD-L1 Therapy:Insights from the CPI-444 Clinical Program.</em> <strong>[[Cancer Discovery]]</strong>.<br><br />
<span style="color: #475569;">[权威点评]：该项具有里程碑意义的研究，首次验证了小分子腺苷拮抗剂在PD-1经治失败患者中的生物学活性。</span><br />
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[2] <strong>[[Corvus]]Clinical Research Update(2025/2026).</strong> <em>Long-term follow-up of Ciforadenant in advanced renal cell carcinoma:Predictive value of the Adenosine Signature.</em> [Academic Review]<br><br />
<span style="color: #475569;">[学术点评]：2026年的最新总结明确了腺苷特征基因检测对优化[[Ciforadenant]]临床应用的决定性意义。</span><br />
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西福拉腺苷 (Ciforadenant) · 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;">[[A2aR]]•[[CD73]]•[[PD-1]]•[[CD39]]•[[ADORA2A]]</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;">治疗组合</td><br />
<td style="padding: 10px 15px; color: #334155;">[[阿替利珠单抗]]•[[派姆单抗]]•[[奥沙利铂]]</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;">关联疾病</td><br />
<td style="padding: 10px 15px; color: #334155;">[[肾细胞癌]]•[[结直肠癌]]•[[非小细胞肺癌]]•[[淋巴瘤]]</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;">竞争对手</td><br />
<td style="padding: 10px 15px; color: #334155;">[[Etrumadenant]]•[[AZD4635]]•[[Nirogacestat]]</td><br />
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