2. Academic Validation
  3. Design, syntheses and evaluations of novel indole derivatives as orally selective estrogen receptor degraders (SERD)

Design, syntheses and evaluations of novel indole derivatives as orally selective estrogen receptor degraders (SERD)

  • Bioorg Med Chem Lett. 2020 Nov 15;30(22):127601. doi: 10.1016/j.bmcl.2020.127601.
Jiaqiang Dong 1,  Tie-Lin Wang 1,  Jianyu Lu 2,  Charles Z Ding 3,  Lihong Hu 4,  Guoping Hu 3,  Huijun He 4,  Xu Zeng 4,  Xiaoting Li 4,  Deheng Sun 3,  Yingjie Zhu 3,  Liang Shen 3,  Qingyang Gu 3,  Chi-Chung Chan 3,  Yuanfeng Xia 3,  Jian Li 3,  Shuhui Chen 3
Affiliations

Affiliations

  • 1 Luoxin Pharmaceutical (Shanghai) Co., Ltd., Building 1 and 1st-3rd Floors, Building 2, No.85 Faladi Road, China (Shanghai) Pilot Free Trade Zone, Shanghai 201210, China.
  • 2 WuXi AppTec (Wuhan), 666 Gaoxin Road, East Lake High-tech Development Zone, Wuhan 430075, China. Electronic address: [email protected].
  • 3 WuXi AppTec (Headquarters), 288 Fute Zhong Road, Waigaoqiao Free Trade Zone, Shanghai 200131, China.
  • 4 WuXi AppTec (Wuhan), 666 Gaoxin Road, East Lake High-tech Development Zone, Wuhan 430075, China.
PMID: 33035677 DOI: 10.1016/j.bmcl.2020.127601
Abstract

Most Estrogen receptor positive (ER +) breast cancers depend on ER signaling pathway to develop. Clinical application of SERD fulvestrant effectively degraded ER, blocked its function and prolonged progression free survival of ER + breast Cancer patients. However, current SERD suffers from limited bioavailability, therefore is given as intramuscular (IM) injection. In this paper, we report herein a novel indole series compounds with nanomolar range ER degradation potencies and oral systemic exposures. Selected compounds suppressed tumor growth in vivo in ER + MCF7 breast Cancer CDX model via p.o. administration. All those data supported further optimizations of this analog to develop preclinical candidate as oral SERD for ER + breast cancer's treatment.

Keywords

Estrogen receptor; Indole; SERD.

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