DABCO ion channel modulators

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DABCO ion channel modulators
DABCO Ion Channel Modulators
Inventors Geoffrey W. Abbott, PhD Department of
Medicine, Weill Cornell
Dr. Abbott is an inventor of US Patent 6,864,364
covering MinK-related genes, important in long QT
syndrome. Investors seek his ion channel
expertise for diligence on drug candidates that
may cause this side effect.
Dr. Engel is an expert organic chemist, and is
the inventor of DABCO, under development as an
anti-infective fabric coating Dr. Rizzo is Dr.
Engels protégé.
And Dr. Robert Engel City University of New
York Dr. Jaimie Lee Rizzo Pace University
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DABCO ion channel modulators
Ion channel modulation in a nutshell
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DABCO ion channel modulators
Market
Pain 27B Epilepsy 13B Multiple
Sclerosis 5B Cancer 15B Other potential
applications, as yet unexplored
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DABCO ion channel modulators
tetraethylammonium (TEA)
DABCO
DiDABCO generalized structure
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Why DABCO?

• Similar to TEA
• Quaternary ammonium ions have historical
  precedent as Kv channel blockers
• Infinitely expandable structural platform
• Quaternization provides the charge necessary for
  activity and can introduce any of a massive range
  of functional groups
• No adverse effects on key cardiac ion channels
• TEA does not show high affinity for hERG or KCNQ1
• As hypothesized, neither do DABCO compounds,
  therefore overcoming the significant hurdle of
  acting on some Kv channels but avoiding key
  drug-induced arrhythmia channels

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Mechanisms of action
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• Developmental Status
• In vitro testing of members of several structural
  classes performed no animal studies yet
• SAR studies underway
• Extracellular blocker binding site identified
• Intellectual Property
• US Patent application pending with broad Markush
  claims
• Availability
• Exclusive licenses available

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Next Steps

• Accelerate evaluation of derivatives in current
  model
• Move to medium or high-throughput screening
• Expand studies to other ion channels
• Other Kv channel subfamilies, other K channels
• TRP channels (pain, cancer)
• neurotransmitter-gated ion channels (pain,
  depression)
• Begin animal studies
• Toxicity testing
• Efficacy in models of pain, cancer, epilepsy, MS
  etc