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6314211 
Journal Article 
Thiochroman derivative CH4986399, a new nonsteroidal estrogen receptor down-regulator, is effective in breast cancer models 
Yoneya, T; Taniguchi, K; Nakamura, R; Tsunenari, T; Ohizumi, I; Kanbe, Y; Morikawa, K; Kaiho, S; Yamada-Okabe, H 
2010 
Yes 
Anticancer Research
ISSN: 0250-7005
EISSN: 1791-7530 
30 
3 
873-878 
English 
20393009 
WOS:000276561300023 
BACKGROUND: Tamoxifen, a selective estrogen receptor modulator, and fulvestrant, a selective estrogen receptor down-regulator (SERD), are now available for estrogen receptor-positive breast cancer patients. However, these patients acquire drug-resistance during the treatments. We identified a new orally active nonsteroidal SERD, CH4986399, which is structurally unrelated to fulvestrant and tamoxifen.

MATERIALS AND METHODS: We examined the oral antitumor activity and down-regulation of ER by CH4986399 in human breast cancer Br-10 and ZR-75-1 xenografts.

RESULTS: In the Br-10 xenografts, CH4986399 (100 mg/kg p.o.) as well as fulvestrant (3 mg/body s.c.) strongly reduced tumor weight. In the ZR-75-1 xenografts, CH4986399 (100 mg/kg p.o.) strongly reduced tumor weight and ER content without agonistic activity. In contrast, tamoxifen (100 mg/kg p.o.) showed only moderate antitumor activity and no ER down-regulation.

CONCLUSION: With a chemical structure different from both fulvestrant and tamoxifen, CH4986399, may help overcome drug resistance from the endocrine treatment sequence for breast cancer patients. 
Breast cancer; orally active; selective estrogen receptor down-regulator SERD; nonsteroidal