Figure 6.

Comparative antitumor activity of PD 168393 and its reversible congener PD 174265 (a) and corresponding modulation of the EGFr phosphotyrosine content (b). •, Control; □, PD 174265; ▾, PD 168393. (a) Athymic nude mice housed in filtered cages were implanted s.c. with a fragment (≈30 mg) of A431 human epidermoid carcinoma and were randomized into treatment groups when the tumors were palpable. Animal dosing and tumor measurement were carried out essentially as described (45). The compounds were suspended in a vehicle containing 4% dimethylacetamide in aqueous 50 mM sodium lactate buffer (pH 4) and delivered i.p. to the mice at 58 mg/kg on days 10–14, 17–21, and 24–28 (shown with arrows) after tumor implant. Bars = mean ± SE. (b) Nude mice bearing 300- to 500-mg A431 tumors were treated with a single 58 mg/kg i.p. dose of either inhibitor or vehicle as described above. At various times after treatment the tumors were excised and ground to a frozen powder with a mortar and pestle chilled with liquid nitrogen. EGFr was extracted (33) and phosphotyrosine content was determined by ELISA (Calbiochem).