A SPECIFIC INHIBITOR OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR TYROSINE KINASE
A SPECIFIC INHIBITOR OF THE EPIDERMAL GROWTH-FACTOR RECEPTOR TYROSINE KINASE
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DOI：
10.1126/science.8066447
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发表时间：
1994-08-19
期刊：
影响因子：
56.9
通讯作者：
BRIDGES, AJ
中科院分区：
文献类型：
--
作者：
FRY, DW;KRAKER, AJ;BRIDGES, AJ
一种名为 PD 153035 的小分子可抑制表皮生长因子 (EGF) 受体酪氨酸激酶，抑制常数为 5 pM。该抑制剂对 EGF 受体酪氨酸激酶具有特异性，并且仅在微摩尔或更高浓度下抑制其他纯化的酪氨酸激酶。 PD 153035 在成纤维细胞或人表皮样癌细胞中以低纳摩尔浓度快速抑制 EGF 受体的自身磷酸化，并选择性阻断 EGF 介导的细胞过程，包括有丝分裂、早期基因表达和致癌转化。 PD 153035 与其他酪氨酸激酶抑制剂相比，对分离的 EGF 受体酪氨酸激酶的抑制效力增加了 4 至 5 个数量级，对细胞磷酸化的抑制效力增加了 3 至 4 个数量级。
A small molecule called PD 153035 inhibited the epidermal growth factor (EGF) receptor tyrosine kinase with a 5-pM inhibition constant. The inhibitor was specific for the EGF receptor tyrosine kinase and inhibited other purified tyrosine kinases only at micromolar or higher concentrations. PD 153035 rapidly suppressed autophosphorylation of the EGF receptor at low nanomolar concentrations in fibroblasts or in human epidermoid carcinoma cells and selectively blocked EGF-mediated cellular processes including mitogenesis, early gene expression, and oncogenic transformation. PD 153035 demonstrates an increase in potency over that of other tyrosine kinase inhibitors of four to five orders of magnitude for inhibition of isolated EGF receptor tyrosine kinase and three to four orders of magnitude for inhibition of cellular phosphorylation.