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Non-ATP dependent inhibitors of extracellular signal-regulated kinase (ERK)
Patent Number: US9115122
 
Executive Summary:
  • Invention Type: Therapeutic
  • Patent Status: Active
  • Patent Link: https://patents.google.com/patent/US9115122/
  • Research Institute: University of Maryland - Baltimore
  • Disease Focus: Melanoma
  • Basis of Invention: Heterocyclic compounds as ERK inhibitors
  • How it works: Heterocyclic compounds in a pharmaceutically acceptable carrier that selectively block ERK1/2, but not other kinases, in contrast with current ATP-competitive inhibitors
  • Lead Challenge Inventor: Paul Shapiro
  • Inventors: Paul S. Shapiro, Alexander D. MacKerell, JR., Steven Fletcher
  • Development Stage: Pre-clinical
  • Novelty:
    • Novel compound to inhibit ERK-pathways, overcoming off-target effects as seen with previously tested inhibitors
  • Clinical Applications:
    • Stand-alone therapeutic or combined with other therapeutics to prevent drug resistance
 
General Description:
ERK1/2 are key drivers of proliferation and survival in cancers, but also play an essential role in normal cellular processes. Several selective ATP-competitive inhibitors of ERK1/2 have been developed, but have not made it to the clinic yet, as they may have toxic off-target effects involving other kinases. In addition, unanticipated activation of the ERK1/2 pathway through alternate mechanisms results in compensatory signaling pathways that lead to drug-resistance. The current invention describes compounds that selectively inhibit ERK-mediated phosphorylation, which may overcome both off-target effects and aid in preventing the activation of drug-resistance pathways.
 
Strengths:
  • Selective
  • May overcome drug resistance in melanomas
  • Less off-target effects
 
Weaknesses:
  • Targets pathway that plays key role in normal cellular processes too
 
Patent Status:
Filing date: 2013-12-20
 
Inventor Bio: Paul Shapiro
http://faculty.rx.umaryland.edu/pshapiro/
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