查看“D-1553”的源代码

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            <strong>[[D-1553]]</strong>（通用名：<strong>[[格里罗西布]]</strong>/<strong>[[Garsorasib]]</strong>）是一款由<strong>[[益方生物]]</strong>自主研发的、具有全球自主知识产权的强效<strong>[[KRASG12C]]</strong>不可逆<strong>[[共价抑制剂]]</strong>。作为<strong>[[国产靶向药物]]</strong>在<strong>[[KRAS]]</strong>领域的领军药物，[[D-1553]]旨在解决既往被认为<strong>[[不可成药]]</strong>的致癌驱动基因突变。临床研究显示，该药物在治疗携带[[KRASG12C]]突变的<strong>[[非小细胞肺癌]]</strong>（[[NSCLC]]）及<strong>[[结直肠癌]]</strong>（[[CRC]]）中展现出优异的<strong>[[抗肿瘤活性]]</strong>和良好的<strong>[[安全性]]</strong>。
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            <div style="font-size: 1.2em; font-weight: bold; letter-spacing: 1.2px;">D-1553</div>
            <div style="font-size: 0.7em; opacity: 0.85; margin-top: 4px;">Drug:[[Garsorasib]] · 点击展开详情</div>
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                <div style="font-size: 0.8em; color: #64748b; margin-top: 12px; font-weight: 600;">强效[[KRASG12C抑制剂]]</div>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0; width: 40%;">主要靶点</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0; color: #b91c1c;"><strong>[[KRASG12C]]</strong></td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[CAS登记号]]</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">2561248-36-8</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子式]]</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">C27H29ClF2N8O</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[分子量]]</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0;">587.02Da</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569; border-bottom: 1px solid #e2e8f0;">[[给药途径]]</th>
                    <td style="padding: 10px 12px; border-bottom: 1px solid #e2e8f0; color: #1e40af;">[[口服]]</td>
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                    <th style="text-align: left; padding: 10px 12px; background-color: #f1f5f9; color: #475569;">[[研发公司]]</th>
                    <td style="padding: 10px 12px;">[[益方生物]]([[InventisBio]])</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：高选择性的共价捕获</h2>
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        [[D-1553]]通过精准设计的分子结构，实现了对[[KRASG12C]]致癌蛋白的<strong>[[异构锁定]]</strong>。
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        <li style="margin-bottom: 12px;"><strong>[[共价结合]]：</strong>[[D-1553]]含有一个高活性的[[亲电]]基团，能特异性地与[[KRASG12C]]突变蛋白12位上的<strong>[[半胱氨酸]]</strong>残基形成共价键。</li>
        <li style="margin-bottom: 12px;"><strong>[[SwitchII]]口袋嵌入：</strong>药物分子嵌入蛋白表面的[[SwitchII]]变构口袋，将[[KRAS]]蛋白维持在<strong>[[GDP结合]]</strong>的非活性状态。</li>
        <li style="margin-bottom: 12px;"><strong>通路级联阻断：</strong>通过使[[KRAS]]失活，显著抑制下游<strong>[[MAPK通路]]</strong>（如[[ERK]]磷酸化）及[[PI3K]]通路的激活。</li>
        <li style="margin-bottom: 12px;"><strong>[[脑渗透性]]优化：</strong>分子结构经过优化，具备良好的<strong>[[血脑屏障]]</strong>穿透能力，可有效应对临床上的<strong>[[脑转移]]</strong>难题。</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;">临床图谱：D-1553-01研究数据矩阵</h2>
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                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #0f172a; width: 25%;">[[癌种]]类型</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #475569;">[[临床表现]]</th>
                <th style="padding: 12px; border: 1px solid #cbd5e1; color: #1e40af;">[[核心结论]]</th>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[非小细胞肺癌]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">在多线治疗失败的患者中，[[ORR]]达40.5%，[[DCR]]达91.9%。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">展现出与国际顶尖药物相当的[[二线治疗]]潜力。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[结直肠癌]]</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">单药及联合[[西妥昔单抗]]方案均观察到明显的肿瘤回缩。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">正在进行的[[联合用药]]试验显示出更强的协同获益。</td>
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                <td style="padding: 10px; border: 1px solid #cbd5e1; font-weight: 600;">[[脑转移]]队列</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">[[颅内缓解率]]优异，部分患者实现颅内病灶[[完全缓解]]。</td>
                <td style="padding: 10px; border: 1px solid #cbd5e1;">有望成为[[肺癌]]脑转移患者的关键靶向药物。</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;">治疗策略：安全性与精准化用药</h2>
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        <li style="margin-bottom: 12px;"><strong>[[精准筛查]]：</strong>临床应用前必须通过<strong>[[NGS]]</strong>（二代测序）或[[PCR]]方法确认患者存在[[KRASG12C]]突变。</li>
        <li style="margin-bottom: 12px;"><strong>[[肝毒性]]预警：</strong>重点监测<strong>[[转氨酶]]</strong>水平。临床数据显示[[D-1553]]的肝安全性整体受控，但仍需遵医嘱定期复查。</li>
        <li style="margin-bottom: 12px;"><strong>[[剂量管理]]：</strong>常见剂量相关[[不良反应]]为腹泻及皮疹。通过<strong>[[剂量调整]]</strong>（减量或暂停）可有效管理毒性。</li>
        <li style="margin-bottom: 12px;"><strong>[[耐药监控]]：</strong>建议在治疗过程中通过<strong>[[液体活检]]</strong>（[[ctDNA]]）监测潜在的旁路激活，如[[MET扩增]]。</li>
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        <h3 style="color: #0f172a; font-size: 1.15em; margin-bottom: 20px; border-bottom: 2px solid #3b82f6; display: inline-block; padding-bottom: 5px;">关键相关概念</h3>
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            <div style="color: #334155;"><strong style="color: #1e40af;">[[格里罗西布]]</strong>：[[D-1553]]的通用名，标志着国产KRAS靶向药进入新阶段。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[益方生物]]</strong>：国内知名的[[创新药物]]研发商，[[D-1553]]的核心研发实体。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[Sotorasib]]</strong>：全球首款KRASG12C抑制剂，是[[D-1553]]的重要参照药物。</div>
            <div style="color: #334155;"><strong style="color: #1e40af;">[[西妥昔单抗]]</strong>：在[[结直肠癌]]中常与[[D-1553]]联用的[[EGFR单抗]]。</div>
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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>Wu YL, et al. (2023).</strong> <em>Efficacy and Safety of D-1553 in Patients with KRAS G12C-Mutated Non-Small Cell Lung Cancer.</em> <strong>[[JTO]]</strong>. 2023;18(11).<br>
            <span style="color: #475569;">[学术点评]：该项多中心研究证实了国产抑制剂在广泛中国人群中的高效性与安全性。</span>
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            [2] <strong>Gao B, et al. (2024).</strong> <em>Pharmacokinetics and initial activity of D-1553 in advanced solid tumors.</em> <strong>[[CCR]]</strong>. 2024.<br>
            <span style="color: #475569;">[学术点评]：揭示了[[D-1553]]卓越的[[药代动力学]]特性及其在脑转移控制中的潜能。</span>
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            [3] <strong>InventisBio Academic Review. (2025).</strong> <em>Next-generation KRAS inhibitors: Garsorasib pipeline update.</em> <strong>[[Academic Review]]</strong>.<br>
            <span style="color: #475569;">[学术点评]：综合分析了[[D-1553]]在联合免疫治疗及克服耐药方面的最新转化医学证据。</span>
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            D-1553 ([[Garsorasib]] / [[格里罗西布]]) · 知识图谱导航
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">核心靶点</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[KRASG12C]] • [[SwitchII口袋]] • [[GDP状态锁定]] • [[MAPK抑制]]</td>
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">临床应用</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[非小细胞肺癌]] • [[结直肠癌]] • [[脑转移]] • [[液体活检]]</td>
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                <td style="width: 100px; background-color: #f8fafc; color: #334155; font-weight: 600; padding: 10px 15px; text-align: left; vertical-align: middle;">研发相关</td>
                <td style="padding: 10px 15px; color: #334155; text-align: left;">[[益方生物]] • [[国产创新药]] • [[D-1553-01]] • [[变构调节]]</td>
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