IC50: 20 and 79 nM for EGFR and c-ErbB2, respectively

EGFR/ErbB2 Inhibitor is an EGFR and c-ErbB2 inhibitor.

EGFR and c-ErbB-2 are members of the epidermal growth factor receptor subfamily of protein tyrosine kinases. Their cellular overexpression causes transformation, so that the cells will grow in the absence of growth factors. An inhibitor of thse kinases should block the receptor signalling, subsequent transformation and inappropriate growth.

In vitro: EGFR/ErbB2 Inhibitor was identified as a potent inhibitor of both c-erbB-2 and EGFr [IC50: 0.079 μM for c-erbB-2, 0.020 μM for EGFr (isolated enzyme), 2.0 μM for HB4aC5.2 cells, 1.2 μM for BT474, both overexpressing c-erbB-2; 2.5 μM for HN5 cells overexpressing EGFr]. This combined potency was contrast to smaller, previously reported anilinoquinazolines and its subsequent analogues [1].

In vivo: GW974, a analog of EGFR/ErbB2 Inhibitor, was evaluated in the fast growing N87 gastric tumour xenograft in SCID mice. Results showed that GW974 at bid dose of 10 mg/kg po led to a 50% inhibition of tumour growth over the 20-day dosing period. Moreover, GW974 at 10 mg/kg po bid had complete inhibition of tumour growth over the 20-day dosing period in the BT474 breast tumour xenograft model. A longer-term study with initial dosing at 30 mg/kg po bid produced tumour shrinkage [1].

Clinical trial: Up to now, EGFR/ErbB2 Inhibitor is still in the preclinical development stage.

Reference:
[1] S.  Cockerill, C. Stubberfield, J. Stables, et al. Indazolylamino quinazolines and pyridopyrimidines as inhibitors of the EGFr and C-erbB-2. Bioorganic & Medicinal Chemistry Letters 11, 1401-1405 (2001).