Copp B R, Fairchild C R, Cornell L, Casazza A M, Robinson S, Ireland C M
Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112, and Bristol-Myers Squibb Pharmaceutical Research Institute, P.O. Box 4000, Princeton, New Jersey 08543, USA.
J Med Chem. 1998 Sep 24;41(20):3909-11. doi: 10.1021/jm980294n.
The known 2-aminoimidazole alkaloid naamidine A (1) was isolated from a Fijian Leucetta sp. sponge as an inhibitor of the epidermal growth factor (EGF) receptor. The compound exhibited potent ability to inhibit the EGF signaling pathway and is more specific for the EGF-mediated mitogenic response than for the insulin-mediated mitogenic response. Evaluation in an A431 xenograft tumor model in athymic mice indicated that naamidine A exhibited at least 85% growth inhibition at the maximal tolerated dose of 25 mg/kg. Preliminary mechanism of action studies indicate that the alkaloid fails to inhibit the binding of EGF to the receptor and has no effect on the catalytic activity of purified c-src tyrosine kinase.
已知的2-氨基咪唑生物碱纳米定A（1）是从斐济的一种白海绵属海绵中分离出来的，作为表皮生长因子（EGF）受体的抑制剂。该化合物表现出强大的抑制EGF信号通路的能力，并且对EGF介导的促有丝分裂反应比对胰岛素介导的促有丝分裂反应更具特异性。在无胸腺小鼠的A431异种移植肿瘤模型中的评估表明，纳米定A在最大耐受剂量25mg/kg时表现出至少85%的生长抑制。初步的作用机制研究表明，该生物碱不能抑制EGF与受体的结合，对纯化的c-src酪氨酸激酶的催化活性也没有影响。
