TY - JOUR T1 - Thiochroman Derivative CH4986399, A New Nonsteroidal Estrogen Receptor Down-regulator, Is Effective in Breast Cancer Models JF - Anticancer Research JO - Anticancer Res SP - 873 LP - 878 VL - 30 IS - 3 AU - TAKAAKI YONEYA AU - KENJI TANIGUCHI AU - RYO NAKAMURA AU - TOSHIAKI TSUNENARI AU - IWAO OHIZUMI AU - YOSHITAKE KANBE AU - KAZUMI MORIKAWA AU - SHIN-ICHI KAIHO AU - HISAFUMI YAMADA-OKABE Y1 - 2010/03/01 UR - http://ar.iiarjournals.org/content/30/3/873.abstract N2 - 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 ER -