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IC50: 370 pM

The EGFR is a 170-kDa protein that contains an extracellular ligand binding domain, a single transmembrane domain, and an intracellular tyrosine kinase domain. EGF-R is hyperactivated in numerous tumors including those derived from the lung, brain, bladder, prostate, head, and neck. It has been shown previously that 4-anilino quinazolines compete with the ability of ATP binding the EGFR, inhibit EGF-stimulated autophosphorylation of tyrosine residues in EGFR, and block EGF-mediated growth. CL-387785 is an irreversible inhibiter of EGFR.

In vitro: CL-387785 covalently bound to EGFR. It also specifically inhibited kinase activity of the protein, blocked EGF-stimulated autophosphorylation of the receptor in cells, inhibited cell proliferation primarily in a cytostatic manner in cell lines that overexpress EGF-R or c-erbB-2 [1].

In vivo: The effects of CL-387785 on tumor growth were assessed in human tumor xenografts implanted s.c. in the flanks of nude mice. CL-387785 inhibited the growth of tumors derived from A431 cells when the drug was administered i.p. or p.o.. Inhibitory effects were observed within 7 days after the onset of therapy. No efficacy was observed with CL-387785 in tumors derived from cell lines that did not overexpress EGF-R, including the human breast carcinoma MDA-MB-435 [1].

Clinical trial: Up to now, CL-387785 is still in the preclinical development stage.

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