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*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

10 Scopus citations

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

Keywords

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

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