In vivo tumor growth inhibition produced by a novel sulfonamide, E7010, against rodent and human tumors.

The search for compounds active against solid tumors has led us to the discovery of a novel sulfonamide, E7010 (N-[2-[(4-hydroxyphenyl)amino]-3-pyridinyl]-4- methoxybenzenesulfonamide), which inhibits tubulin polymerization. When administered orally, E7010 showed good antitumor activity against various rodent tumors and human tumor xenografts. In tests on mouse tumor, E7010, administered in doses of 25-100 mg/kg daily for 8 days, inhibited the growth of colon 38 carcinoma inoculated s.c. in mice by 60-99%. E7010 was active against s.c. inoculated M5076 fibrosarcoma (75% tumor growth inhibition), s.c. inoculated Lewis lung carcinoma (84% increase in life span), and i.p. inoculated P388 leukemia (118% increase in life span). In a test on rat tumor, E7010 inhibited the growth of SST-2 mammary carcinoma inoculated s.c. in rats by 84%. In tests on s.c. inoculated human tumor xenografts, E7010, when administered orally, showed a broad spectrum of activity. E7010 inhibited the growth of: four kinds of gastric cancer, H-81, H-111, SC-2, and SC-6 by 60-78%; three kinds of colon cancer, H-143, COLO320DM, and WiDr by 58-83%; three kinds of lung cancer, LC-376, LC-6, and LX-1 by 63-82%; and two kinds of breast cancer, H-31 and MX-1 by 79-87%. In studies on drug-resistant P388 leukemia, E7010 was effective against vincristine-resistant P388, cisplatin-resistant P388, and 5-fluorouracil-resistant P388 sublines in mice. Because of its good activity against rodent tumors and human tumor xenografts, E7010 is currently undergoing Phase I clinical trials.