Thiochroman derivative CH4986399, a new nonsteroidal estrogen receptor down-regulator, is effective in breast cancer models.

Abstract

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.

• Authors: Takaaki Yoneya, Kenji Taniguchi, Ryo Nakamura, Toshiaki Tsunenari, Iwao Ohizumi, Yoshitake Kanbe, Kazumi Morikawa, Shin-Ichi Kaiho, Hisafumi Yamada-Okabe
• Journal: Anticancer research (Anticancer Res) Vol. 30 Issue 3 Pg. 873-8 (Mar 2010) ISSN: 1791-7530 [Electronic] Greece
• PMID: 20393009 (Publication Type: Journal Article)

Chemical References

• Bridged Bicyclo Compounds, Heterocyclic
• CH 4986399
• Receptors, Estrogen
• Selective Estrogen Receptor Modulators

Topics

• Animals
• Breast Neoplasms (drug therapy, metabolism, pathology)
• Bridged Bicyclo Compounds, Heterocyclic (pharmacology)
• Cell Line, Tumor
• Down-Regulation (drug effects)
• Female
• Humans
• Mice
• Mice, Nude
• Receptors, Estrogen (biosynthesis)
• Selective Estrogen Receptor Modulators (pharmacology)
• Xenograft Model Antitumor Assays