Yaish P, Gazit A, Gilon C, Levitzki A
Department of Biological Chemistry, Hebrew University of Jerusalem, Israel.
Science. 1988 Nov 11;242(4880):933-5. doi: 10.1126/science.3263702.
A systematic series of low molecular weight protein tyrosine kinase inhibitors were synthesized; they had progressively increasing affinity over a 2500-fold range toward the substrate site of epidermal growth factor (EGF) receptor kinase domain. These compounds inhibited EGF receptor kinase activity up to three orders of magnitude more than they inhibited insulin receptor kinase, and they also effectively inhibited the EGF-dependent autophosphorylation of the receptor. The most potent compounds effectively inhibited the EGF-dependent proliferation of A431/clone 15 cells with little or no effect on the EGF-independent proliferation of these cells. The potential use of tyrosine protein kinase inhibitors as antiproliferative agents is demonstrated.
合成了一系列低分子量蛋白酪氨酸激酶抑制剂；它们对表皮生长因子（EGF）受体激酶结构域的底物位点的亲和力在2500倍的范围内逐渐增加。这些化合物抑制EGF受体激酶活性的程度比抑制胰岛素受体激酶的程度高出三个数量级，并且它们还有效地抑制了受体的EGF依赖性自身磷酸化。最有效的化合物有效地抑制了A431/克隆15细胞的EGF依赖性增殖，而对这些细胞的EGF非依赖性增殖几乎没有影响。证明了酪氨酸蛋白激酶抑制剂作为抗增殖剂的潜在用途。
