An EGFR inhibitor
BIBX1382 is a potent, selective inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase with IC50 value of 3 nM.[1]
BIBX1382 is an inhibitor of EGFR kinase for treatment of cancer. In a tyrosine kinase activity assay using cytoplasmic tyrosine kinase domains of EGFR, HER2, VEGFR2, HGFR, IGF1R, B-InsRK and c-src cloning and expressing in Sf9 insect cells, BIBX1382 selectively and potently inhibited EGFR kinase activity with an IC50 value of 3 nM. In the EGFR and pEGFR ELISA assay using EGFR highly expressed A431 cells (vuval squamous cell carcinoma), BIBX1382 inhibited EGFR phosphorylation at EC50 at 141 nM.[1] In A431, FaDu (hypopharyngeal squamous cell carcinoma) and HN5 (head and neck squamous cell carcinoma) xenograft nude mice models, oral administration of BIBX1382 at dose of 10 mg/kg daily showed strong antitumor activity in a dose-dependent manner after 2 weeks of treatment. Moreover, tumor regressions were obtained after 170 days’ long term oral administration of BIBX1382 at dose of 50 mg/kg daily in A431 xenograft nice model.[1]
参考文献:
1.?F. F. Solca, A. Baum, E. Langkopf, G. Dahmann, K. H. Heider, F. Himmelsbach and J. C. van Meel, J Pharmacol Exp Ther 2004, 311, 502-509.
Animal experiment: | Animal administration[1]Five- to six-week-old athymic NMRI-nu/nu female mice (21-31 g) were inoculated s.c. with 1 × 106 (in 100 μl) A431, FaDu, or HN5 cells into the right flank of the animal. After 7 to 11 days, tumors reached a average volume of 40 to 130 mm3. The mice were randomized and treated daily p.o. with Falnidamol (BIBX 1382), BIBU1361, or vehicle control on the basis of individual weights. Tumors were measured three times a week with calipers, and tumor volumes were calculated by the formula π/6 × length × (width)2. Experimental compounds were prepared in 25% aqueous hydroxypropyl-β-cyclodextrin and administered by intragastral gavage. The administration volume was 10 ml/kg b.wt. |
参考文献: [1]. Solca FF, et al. Inhibition of epidermal growth factor receptor activity by two pyrimidopyrimidine derivatives. J Pharmacol Exp Ther. 2004 Nov;311(2):502-9. | |
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