In:
Cancer Research, American Association for Cancer Research (AACR), Vol. 74, No. 19_Supplement ( 2014-10-01), p. 2707-2707
Abstract:
Background: ER-α36, a novel truncated variant of estrogen receptor α, was recently discovered and extensively studied as a potential therapeutic target. ER-α36 was found to be overexpressed in many cancers including estrogen-positive and negative breast cancer, lung cancer, prostate cancer, endometrial cancer, liver cancer and other cancers. This suggests that ER-α36 is potentially a promising target for the development of novel anticancer agents with broader clinical applications. This study aims to evaluate the in vitro and in vivo performance of SNG1153, an orally available, synthetic modulator of ER-α36. Methods: the viabilities of ER-α36 overexpressed cancer cells were evaluated using a CCK-8 assay after exposure to SNG1153. Pharmacokinetic study was conducted in rat and SNG1153 was administered orally in escalated doses. In-vivo efficacies of SNG1153 were evaluated in Bcap-37 xenograft model, Ishikawa xenograft model and SPC-A-1 xenograft model. Results: SNG1153 showed significant inhibition at low micromolar concentrations in ER-α36 overexpressed cell lines including the one resistant to tamoxifen. SNG1153 exhibited a linear PK profile with a bioavailability of more than 55% in the rat PK study. In the in-vivo efficacy studies, 3 doses were investigated and SNG1153 showed dose-dependent inhibition. The tumor growth inhibition at high dose was 57% in the breast cancer Bcap-37 xenograft model, 65% in the endometrial cancer Ishikawa xenograft model and 52% in lung adenocarcinoma SPC-A-1 xenograft model. No signs of toxicity were observed in these models. Conclusion: SNG1153, as a synthetic ER-α36 modulator, showed promising activities in many in vitro and in vivo models. It is currently in preclinical development stage. Citation Format: Bo Zhang, Kun Meng, Xiao Shang, Zhaoyi Wang, Yanzhong Zhang, Fang Fang, Jing Wang, Zonghui Wang, Jun Wang, Yuming Guo, Shiyang Liu, Feng Chen, Hongxia Ding, Jiancun Zhang, Jun Bao. In vitro and in vivo evaluation of SNG1153, a synthetic modulator of ER-α36. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2707. doi:10.1158/1538-7445.AM2014-2707
Type of Medium:
Online Resource
ISSN:
0008-5472
,
1538-7445
DOI:
10.1158/1538-7445.AM2014-2707
Language:
English
Publisher:
American Association for Cancer Research (AACR)
Publication Date:
2014
detail.hit.zdb_id:
2036785-5
detail.hit.zdb_id:
1432-1
detail.hit.zdb_id:
410466-3
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