Background:

4-methyl Erlotinib is an analog of erlotinib by the addition of a methyl group at the four position of the phenyl group. Erlotinib is a tyrosine kinase inhibitor which acts on the epidermal growth factor receptor (EGFR) [1].

The epidermal growth factor receptor (EGFR) autocrine pathway has been important for cancer development and progression, including cell proliferation, apoptosis, angiogenesis, and metastatic spread [2].

Erlotinib inhibits EGFR-associated kinase activity by binding to the EGF-activated receptor, with the phenyl group at one end sequestered in a hydrophobic pocket of the kinase domain and the ether linkages at the opposite end projecting into solvent [1].

Erlotinib can prolong survival in patients with non–small-cell lung cancer after first-line or second-line chemotherapy [3].

参考文献:
[1] Stamos, J. ,Sliwkowski, M.X. and Eigenbrot, C. Structure of the epidermal growth factor receptor kinase domain alone and in complex with a 4-anilinoquinazoline inhibitor. The Journal of Biological Chemisty 277(48), 46265-46272 (2002).
[2] Ciardiello F, Tortora G.  A novel approach in the treatment of cancer: targeting the epidermal growth factor receptor[J]. Clinical Cancer Research, 2001, 7(10): 2958-2970.
[3] Shepherd F A, Rodrigues Pereira J, Ciuleanu T, et al.  Erlotinib in previously treated non–small-cell lung cancer[J]. New England Journal of Medicine, 2005, 353(2): 123-132.