2. Academic Validation
  3. New Selective Inhibitors of ERG Positive Prostate Cancer: ERGi-USU-6 Salt Derivatives

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

  • ACS Med Chem Lett. 2021 Oct 19;12(11):1703-1709. doi: 10.1021/acsmedchemlett.1c00308.
Binil Eldhose 1 2,  Mallesh Pandrala 3 3 4,  Charles Xavier 1 2,  Ahmed A Mohamed 1 2,  Shiv Srivastava 1,  Anu D Sunkara 1 5,  Albert Dobi 1 2,  Sanjay V Malhotra 3 3 4
Affiliations

Affiliations

  • 1 Center for Prostate Disease Research, Murtha Cancer Center Research Program, Department of Surgery, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20889, United States.
  • 2 Henry M. Jackson Foundation for the Advancement of Military Medicine, Inc., Bethesda, Maryland 20817, United States.
  • 3 Department of Cell, Developmental and Cancer Biology, Center for Experimental Therapeutics, Knight Cancer Institute, Oregon Health and Science University, Portland, Oregon 97201, United States.
  • 4 Division of Radiation & Cancer Biology, Department of Radiation Oncology, Stanford University School of Medicine, Stanford, California 94305, United States.
  • 5 Washington Adventist University, Takoma Park, Maryland 20912, United States.
PMID: 34790292 DOI: 10.1021/acsmedchemlett.1c00308
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.

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