Icotinib Hydrochloride

Icotinib Hydrochloride是上皮生长因子受体酪氨酸激酶(EGFR-TKI)的高效高选择性抑制剂，其IC50值为5 nM。

EGFR是一种癌症驱动蛋白，在正常细胞和癌细胞的表面表达[1]，体细胞突变特别是外显子19缺失或外显子21 L858R突变的病人的酪氨酸激酶域存在激活突变，导致不受控制的细胞增殖[2]。在多种类型的癌症中发现，EGFR过表达引起抗凋亡Ras信号通路不正常活化[3]。

Icotinib是喹唑啉衍生物，可逆的结合到EGFR蛋白的ATP结合位点，阻止信号转导级联反应[4]。Icotinib抑制胞内上皮生长因子受体（EGFR）相关酪氨酸激酶（TK）的磷酸化[5]。

Icotinib用于EGFR突变阳性、晚期或转移性非小细胞肺癌（NSCLC）病人的二线或三线治疗，这些病人经历过至少一次施用含铂药物化疗失败[6]。

参考文献：
1. A Douglas Laird,and Julie M Cherrington. Small molecule tyrosine kinase inhibitors: clinical development of anticancer agents. 2003, 12(1): 51-64.
2. Raymond E, Faivre S, Armand JP: Epidermal growth factor receptor tyrosine kinase as a target for anticancer therapy. Drugs. 2000;60 Suppl 1:15-23.
3. Sordella,R. "Gefitinib-Sensitizing EGFR Mutations in Lung Cancer Activate Anti-Apoptotic Pathways". Science ,2004, 305 (5687): 1163-1167.
4. Bulgaru AM. et al. Erlotinib (Tarceva): a promising drug targeting epidermal growth factor receptor tyrosine kinase. Expert Rev Anticancer Ther. 2003 Jun;3(3):269-79.
5. Dudek AZ.et al. Skin rash and bronchoalveolar histology correlates with clinical benefit in patients treated with gefitinib as a therapy for previously treated advanced or metastatic non-small cell lung cancer. Lung Cancer. 2006, 51(1):89-96.
6. C Delbaldo, S Faivre, E Raymond. Les inhibiteurs des récepteurs de l’Epidermal Growth Factor (EGF) Epidermal growth factor inhibitors. La Revue de Médecine Interne. 2003,24(6): 372–383.