Erlotinib mesylate (R 1415; CP-358774; OSI-774)is a directly acting inhibitor of human EGFR tyrosine kinase with an IC50 of 2 nM.
IC50 Value: 2 nM [1]
in vitro: CP-358,774 inhibits the proliferation of DiFi human colon tumor cells at submicromolar concentrations in cell culture and blocks cell cycle progression at the G1 phase. This inhibitor produces a marked accumulation of retinoblastoma protein in its underphosphorylated form and accumulation of p27KIP1 in DiFi cells, which may contribute to the cell cycle block [1]. Erlotinib increased NOX4 mRNA and protein expression by increasing its promoter activity and mRNA stability in FaDu cells [2].
in vivo: At doses of 100 mg/kg, CP-358,774 completely prevents EGF-induced autophosphorylation of EGFR in human HN5 tumors growing as xenografts in athymic mice and of the hepatic EGFR of the treated mice [1]. Erlotinib had no single agent antitumor activity, raised serum-VEGF levels, and lacked a synergistic effect in combination with sorafenib [3].
Toxicity: The most common adverse event was skin disorder, followed by diarrhea. Although 45.6% of the patients in this study received erlotinib as a fourth-line or subsequent treatment, the results from this study were similar to those of clinical studies [4].
Clinical trial: A Safety Study in Patients With Advanced Solid Tumors. Phase 1

AEE788
Afatinib
Afatinib dimaleate
AG 18
AG-1478