PD 173074

PD 173074（CAS 号 219580-11-7）是一种高选择性酪氨酸激酶抑制剂，核心生物学功能为抑制成纤维细胞生长因子受体（FGFR）和血管内皮生长因子受体 2（VEGFR2）活性，阻断相关信号通路介导的血管生成、肿瘤细胞增殖与转移，还可逆转 ABCB1/ABCC10 介导的多药耐药，同时在精神分裂症相关研究中显示与 FGFR1 存在高亲和力结合潜力；作用靶点及类型为抑制FGFR1（主要靶点）、FGFR3 及 VEGFR2 的酪氨酸激酶活性（ATP 竞争性结合 FGFR1 的 ATP 结合口袋），拮抗FGF-2 介导的生物学效应，对 PDGFR、c-Src、EGFR、胰岛素受体等其他激酶选择性低。

关键活性数据：FGFR1 结合 IC₅₀ 21.5±0.8 nM、功能 cAMP IC₅₀ 15.7±5.4 nM，小鼠 FGFR1 IC₅₀ 122 nM、大鼠 727±350 nM、恒河猴 55.5 nM，VEGFR2 自磷酸化抑制 IC₅₀ 100-200 nM，PDGFR IC₅₀ 17.6±1.9 μM、c-Src IC₅₀ 19.8±2.3 μM，EGFR 及胰岛素受体 IC₅₀均 > 50 μM。

动物造模常用于模型治疗，常见模型包括小鼠角膜血管生成模型（评估 FGF/VEGF 诱导的血管生成抑制）、人 GCGR 转基因小鼠急性胰高血糖素挑战模型、结直肠癌异种移植模型、头颈部鳞状细胞癌（HNSCC）相关模型及精神分裂症相关模型。

常用应用与浓度：细胞培养中，CHO-hGCGR 细胞 nM 级浓度用于受体结合与功能实验，HNSCC 细胞系（如 A253、CAL-27 等）用于药物敏感性检测，ABCB1 过表达细胞系（如 HEK293、人表皮癌耐药亚系）100 μM 级浓度用于多药耐药逆转实验；动物实验中，小鼠腹腔注射 1-2 mg/kg/d 用于角膜血管生成抑制，口服 3-30 mg/kg 用于肿瘤相关模型治疗；有效治疗浓度：动物实验中 1 mg/kg/d 可抑制 86% FGF 诱导的血管生成、2 mg/kg/d 可抑制 81% VEGF 诱导的血管生成，细胞层面 nM 级浓度可显著抑制 FGFR1/VEGFR2 活性，100 μM 级浓度可逆转 ABCB1 介导的紫杉醇、长春碱耐药，HNSCC 细胞中特定 CpG 位点甲基化状态与药物敏感性相关，低甲基化细胞对其更敏感。

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