RT Journal Article SR Electronic T1 Thiochroman Derivative CH4986399, A New Nonsteroidal Estrogen Receptor Down-regulator, Is Effective in Breast Cancer Models JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 873 OP 878 VO 30 IS 3 A1 TAKAAKI YONEYA A1 KENJI TANIGUCHI A1 RYO NAKAMURA A1 TOSHIAKI TSUNENARI A1 IWAO OHIZUMI A1 YOSHITAKE KANBE A1 KAZUMI MORIKAWA A1 SHIN-ICHI KAIHO A1 HISAFUMI YAMADA-OKABE YR 2010 UL http://ar.iiarjournals.org/content/30/3/873.abstract AB 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. Copyright© 2010 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved