Afatinib (dimaleate)

Afatinib (BIBW 2992) dimaleate is an orally active, potent and irreversible dual specificity inhibitor of ErbB family (EGFR and HER2), with IC₅₀ values of 0.5 nM, 0.4 nM, 10 nM and 14 nM for EGFR^wt, EGFR^L858R, EGFR^L858R/T790M and HER2, respectively. Afatinib dimaleate can be used for the research of esophageal squamous cell carcinoma (ESCC), non-small cell lung cancer (NSCLC) and gastric cancer^[1][2][3][4]. IC50 & Target: IC50: 0.5 nM (EGFR^wt), 0.4 nM (EGFR^L858R), 10 nM (EGFR^L858R/T790M), 14 nM (HER2), 13000 nM (HGFR), >4000 nM (c-SRC), >100 000 nM (β-InsRK), >100 000 nM (VEGFR-2)^[1] In Vitro: Afatinib dimaleate (100 nM) sufficiently prevents heregulin-stimulated HER3 phosphorylation^[1].
Afatinib dimaleate (0-10000 nM) effectively inhibits anchorage-independent proliferation of NIH-3T3 cells ectopically expressing EGFR mutants, and inhibits cell proliferation of H1666, H3255, and NCI 1975 cells^[1].
Afatinib dimaleate (48-72 h)shows growth inhibition in HKESC-1, HKESC-2, SLMT-1 and EC-1 cells^[2].
Afatinib dimaleate (0-1 μM, 24-48 h) inhibits AKT and MAPK pathways, and inhibits EGFR and AKT phosphorylation in ESCC cell lines^[2].
Afatinib dimaleate (0-1 μM, 16-48 h) induces G0/G1 cell cycle arrest in HKESC-2 and EC-1^[2].
Afatinib dimaleate (0-1 μM, 24-48 h) effectively induces apoptotic cell death in HKESC-2 and EC-1^[2]. In Vivo: Afatinib dimaleate (0-20 mg/kg, Orally, daily for 25 days) shows dramatic tumor regression and downregulation of EGFR, HER2, HER3 and AKT phosphorylation^[1].
Afatinib dimaleate (15 mg/kg, Orally, in a schedule of 5 days on plus 2 days off, for two weeks) strongly inhibits the growth of HKESC-2 tumor^[2].