Discovery and preclinical profile of LX-039, a novel indole-based oral selective estrogen receptor degrader (SERD)

Bioorg Med Chem Lett. 2022 Jun 15:66:128734. doi: 10.1016/j.bmcl.2022.128734. Epub 2022 Apr 15.

Abstract

We previously described the discovery of a novel indole series compounds as oral SERD for ER positive breast cancer treatment. Further SAR exploration focusing on substitutions on indole moiety of compound 12 led to the discovery of a clinical candidate LX-039. We report herein its profound anti-tumor activity, desirable ER antagonistic characteristics combined with favorable pharmacokinetic and preliminary safety properties. LX-039 is currently in clinical trial (NCT04097756).

Keywords: Estrogen receptor; Indole; SERD.

MeSH terms

  • Administration, Oral
  • Breast Neoplasms* / drug therapy
  • Breast Neoplasms* / pathology
  • Clinical Trials as Topic
  • Estrogen Receptor alpha
  • Female
  • Humans
  • Indoles / pharmacology
  • Indoles / therapeutic use
  • Receptors, Estrogen*
  • Selective Estrogen Receptor Modulators / pharmacology

Substances

  • Estrogen Receptor alpha
  • Indoles
  • Receptors, Estrogen
  • Selective Estrogen Receptor Modulators

Associated data

  • ClinicalTrials.gov/NCT04097756