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GH55 - 版本历史
2026-04-19T00:04:25Z
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2026-01-16T05:27:14Z
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<strong>[[GH55]]</strong>是一种由<strong>[[勤浩医药]]</strong>（[[Genhouse Bio]]）自主研发的新型、高效、高选择性口服小分子<strong>[[ERK1/2]]</strong>（[[细胞外信号调节激酶]]）抑制剂。作为[[RAS/RAF/MEK/ERK]]信号通路的终末关键激酶抑制剂，[[GH55]]通过独特的双重抑制机制，不仅能抑制[[ERK1/2]]的催化活性，还能阻断其被上游[[MEK]]磷酸化激活。该药物旨在治疗携带[[MAPK]]信号通路突变（如[[KRAS]]、[[NRAS]]、[[BRAF]]突变）的晚期[[实体瘤]]，特别是为解决临床上由[[RAF]]或[[MEK]]抑制剂引发的反馈性激活及获得性耐药提供了创新方案。<br />
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<div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">[[GH55]]</div><br />
<div style="font-size: 0.75em; opacity: 0.85; margin-top: 4px;">[[ERK1/2]]抑制剂 · 点击展开</div><br />
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<div style="padding: 12px; border: 1px solid #e2e8f0; border-radius: 8px; background: #fff; display: inline-block;"><br />
<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;">[[GH55]]与[[ERK]]激酶结构域结合模型</div><br />
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<div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">核心靶点：[[ERK1]] / [[ERK2]]</div><br />
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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><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">5594 / 5595</td><br />
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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><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[小分子靶向药]]</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[UniProt]]</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">P27361 / P28482</td><br />
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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><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">约 478.5 Da</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">给药途径</th><br />
<td style="padding: 8px 12px; border-bottom: 1px solid #e2e8f0; color: #0f172a;">口服 (胶囊/片剂)</td><br />
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<th style="text-align: left; padding: 8px 12px; background-color: #f1f5f9; color: #475569;">开发公司</th><br />
<td style="padding: 12px; color: #0f172a;">[[勤浩医药]] (Genhouse)</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：双重拦截ERK信号传导</h2><br />
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[[GH55]]通过一种差异化的药理学设计，实现了对[[MAPK]]通路的“垂直封锁”：<br />
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<li style="margin-bottom: 12px;"><strong>催化活性抑制：</strong>[[GH55]]直接结合在[[ERK1/2]]激酶的活性位点，阻断其对下游底物（如[[RSK]]、[[Elk-1]]、[[c-Fos]]等）的磷酸化作用，从而抑制细胞增殖基因的转录。</li><br />
<li style="margin-bottom: 12px;"><strong>磷酸化激活阻断：</strong>通过特定的变构或结合构象，[[GH55]]能够干扰上游[[MEK]]对[[ERK]]的物理接触，防止[[ERK]]在活化环处被磷酸化，从而将[[ERK]]维持在非活化状态。</li><br />
<li style="margin-bottom: 12px;"><strong>克服负反馈代偿：</strong>在携带[[RAF/MEK]]抑制剂耐药突变的肿瘤中，[[ERK]]常作为代偿激活的交汇点。[[GH55]]作为通路的终末节点抑制剂，能有效拦截所有上游信号导致的[[ERK]]异常活化。</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;">临床评价矩阵：GH55 治疗潜力</h2><br />
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<th style="padding: 10px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">目标适应症</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #475569;">分子特征背景</th><br />
<th style="padding: 10px; border: 1px solid #cbd5e1; color: #1e40af;">临床研究现状</th><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[结直肠癌]]/[[肺癌]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">[[KRAS]] / [[NRAS]] 突变</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">正在进行 [[I/II期]] 剂量递增与扩展研究，观察其单一用药及联用效能。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">[[黑色素瘤]]</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">[[BRAF V600]] 突变且经治失败</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">旨在克服第一代 [[BRAFi]] 或 [[MEKi]] 导致的获得性耐药。</td><br />
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<td style="padding: 8px; border: 1px solid #cbd5e1; font-weight: 600;">晚期实体瘤</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">[[MAPK]]通路其他激活变异</td><br />
<td style="padding: 8px; border: 1px solid #cbd5e1;">评估 [[GH55]] 在多瘤种中的安全性、耐受性及 [[PK/PD]] 谱。</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：精准分层与毒性闭环</h2><br />
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[[GH55]]的临床应用侧重于通路全阻断及安全性平衡：<br />
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<li style="margin-bottom: 12px;"><strong>伴随诊断：</strong>患者筛选需基于[[NGS]]检测。识别[[RAS/RAF]]突变状态是判断其是否为[[GH55]]优势人群的前提。</li><br />
<li style="margin-bottom: 12px;"><strong>垂直联合用药：</strong>探索[[GH55]]联合[[SHP2抑制剂]]或[[KRAS G12C抑制剂]]的潜力。通过对通路上下游的同步打击，最大限度降低肿瘤发生克隆演化的概率。</li><br />
<li style="margin-bottom: 12px;"><strong>不良反应监控：</strong>需重点关注[[MAPK]]通路抑制剂共有的[[皮疹]]、[[胃肠道毒性]]及[[磷酸激酶]]（CK）升高。临床推荐采用阶梯式剂量管理。</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>[[ERK1/2]]：</strong>即[[MAPK3]]/[[MAPK1]]，是[[RAS]]通路的执行终点，调控数百种转录因子的活性。</li><br />
<li style="margin-bottom: 8px;"><strong>[[MAPK信号通路]]：</strong>肿瘤生物学中最经典的研究领域，涉及生长因子介导的级联反应。</li><br />
<li style="margin-bottom: 8px;"><strong>[[勤浩医药]]：</strong>一家专注于开发全球新一代小分子抗肿瘤药物的创新药企，[[GH55]]为其管线中的重要资产。</li><br />
<li style="margin-bottom: 8px;"><strong>[[获得性耐药]]：</strong>指肿瘤在治疗过程中通过新突变或旁路激活产生的对药物的不敏感性。</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>Genhouse Bio. (2022).</strong> <em>CDE accepts the IND application of Genhouse's ERK1/2 inhibitor GH55.</em> <strong>[[Official Press Release]]</strong>.[Academic Review]<br><br />
<span style="color: #475569;">[核心价值]：披露了GH55具有优异的代谢性质和极大的安全窗，是一个极具潜力的小分子药物。</span><br />
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[2] <strong>ClinicalTrials.gov. (2024).</strong> <em>A Study on the Safety and Efficacy of GH55 in Patients with MAPK Mutant Advanced Solid Tumors (NCT06310382).</em> <strong>[[NIH Clinical Trials]]</strong>.<br><br />
<span style="color: #475569;">[数据支撑]：正在进行的跨多中心临床试验将为GH55在MAPK变异患者中的临床获益提供决定性证据。</span><br />
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[[GH55]] ([[ERK1/2]]抑制剂) 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;">[[ERK1]]•[[ERK2]]•[[MEK]]•[[KRAS]]•[[BRAF]]•[[SHP2]]</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;">同类/竞争</td><br />
<td style="padding: 10px 15px; color: #334155;">[[Ulixertinib]]•[[BVD-523]]•[[JSI-1187]]</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;">[[勤浩医药]]•[[NMPA]]•[[FDA]]•[[苏州工业园区]]</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;">前沿方向</td><br />
<td style="padding: 10px 15px; color: #334155;">[[针对胰腺癌的垂直抑制研究]]•[[克服MEK抑制剂引发的反馈代偿]]•[[联合免疫检查点抑制剂探索]]</td><br />
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