New Selective Inhibitors of ERG Positive Prostate Cancer: ERGi-USU-6 Salt Derivatives

Binil Eldhose, Mallesh Pandrala, Charles Xavier, Ahmed A. Mohamed, Shiv Srivastava, Anu D. Sunkara, Albert Dobi, Sanjay V. Malhotra

Research output: Contribution to journalArticlepeer-review

Abstract

Prostate cancer is among the leading causes of cancer related death of men in the United States. The ERG gene fusion leading to overexpression of near full-length ERG transcript and protein represents most prevalent (50-65%) prostate cancer driver gene alterations. The ERG oncoprotein overexpression persists in approximately 35% of metastatic castration resistant prostate cancers. Due to the emergence of eventual refractoriness to second- and third-generation androgen axis-based inhibitors, there remains a pressing need to develop drugs targeting other validated prostate cancer drivers such as ERG. Here we report the new and more potent ERG inhibitor ERGi-USU-6 developed by structure-activity studies from the parental ERGi-USU. We have developed an improved procedure for the synthesis of ERGi-USU-6 and identified a salt formulation that further improves its activity in biological assays for selective targeting of ERG harboring prostate cancer cells.

Original languageEnglish (US)
Pages (from-to)1703-1709
Number of pages7
JournalACS Medicinal Chemistry Letters
Volume12
Issue number11
DOIs
StatePublished - Nov 11 2021

Keywords

  • ERG
  • Inhibitor
  • Metastatic castration resistant prostate cancer
  • Oncogene
  • Precision medicine
  • Prostate cancer
  • RIOK2
  • SAR
  • Small molecule
  • TMPRSS2-ERG

ASJC Scopus subject areas

  • Biochemistry
  • Drug Discovery
  • Organic Chemistry

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