Status: Need is Closed

Demonstrating In Vivo Drug Candidate Engagement with Ion Channel Targets

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, through its research unit Neusentis, seeks to collaborate with leading academic and biotechnology companies in Asia who have novel methodologies that can be used in vivo to determine if small molecule drug candidates have engaged selectively with their ion channel target at the intended site of action.


Although Pfizer is specifically interested in ion channel targets involved in pain signalling, the ability to measure engagement with ion channel targets for other therapeutic indications may also be considered.


iStock_000021200790XSmall[1].JPGKey Success Criteria:

Successful proposals must:

    1. Provide a quantifiable measure of drug candidate interaction with a target ion channel, utilizing protocols that are preferably non-invasive and can be translated for use in human subjects participating in clinical trials (or in in vivo animal model surrogates at a minimum).
    2. The proposed methodology needs to distinguish between specific interaction with an ion channel target of interest and non-specific interactions with other ion channels or non-target proteins.
    3. The proposed methodology should be able to be employed to measure target engagement throughout the body, including, but not limited to, deep tissues within the central and peripheral nervous system. Sensory neurones, spinal cord and/or brain are the areas of highest priority.
    4. The proposed methodology should ideally be applicable across the entire family of ion channel proteins/drug targets. However, methodologies that can be used to quantify engagement with specific ion channel classes associated with neuroexcitatory disorders (e.g. pain, epilepsy, etc) are of primary interest.



Drugs that engage with and modulate ion channel function are important therapeutics for treatment of human cardiovascular disorders (angina, hypertension and cardiac arrhythmias), metabolic dysfunction (type II diabetes), and neurological disorders (pain and epilepsy). Pfizer believes that the development of new medicines that target ion channels would be considerably less challenging if it were possible to readily demonstrate/ measure the engagement of the drug candidate with its ion channel target in vivo during clinical trials.


Pfizer is a global leader in pain medicines with products in each of the major classes. Neusentis, our research unit based in Cambridge UK and Research Triangle Park, North Carolina, USA, is focused on discovering new drugs that modulate ion channels as potential therapeutics for pain and sensory disorders.  Although PET imaging studies can demonstrate direct engagement of many drugs to many targets, PET is largely unsuccessful when applied to ion channel drugs.


Possible Approaches:

Neusentis is developing therapeutics that target ion channels expressed in peripheral and central nervous systems (including sensory neurones and the dorsal horn of the spinal cord).


Neusentis would be particularly interested in in vivo methodologies that quantify the engagement of candidate therapeutic agents with their ion channel targets in these tissue regions.


Approaches Not of Interest:

Methodologies that measure a functional consequence of a stimulus (i.e., the perception of pain measured on a pain scale or a quantitative physiological response to pain fiber activation) are not of interest.  Rather, we are seeking direct biophysical evidence of ligand engagement with the target channel.


In developing responses to this Need, please keep in mind that the following list of potential solutions related to pain drug candidates have previously been considered and rejected, due to key limitations. Submitted solutions that include these methodologies will only be considered if evidence is provided describing how these limitations can be overcome.

      1. fMRI assesses the CNS consequences of peripheral pain perception rather than direct ion channel engagement
      2. Capsaicin/cinnamaldehyde flare endpoints identify peripheral functional consequence of nociceptor activation
      3. Threshold tracking is a functional consequence of target engagement and cannot be specifically applied to pain carrying neurons
      4. Microneurography is currently too slow for clinical application
      5. Functional pain endpoints, including sensitized pain endpoints (for example, but not limited to: quantitative sensory testing (QST), heat, cold, electrical, capsaicin, hypotonic fluids, mechanical, UV-induced).


How to Respond:

We are looking for a completed Response Template, which may contain a concise abstract/executive summary. The proposal should briefly describe the technical approach and provide information on technology performance, background and description of the responding team and their related experience. To Respond, please use the red Respond Now button located to the right. Please note that only non-confidential information can be accepted.


By submitting a response you represent that the response does not contain and will not be deemed to contain any confidential information of any kind whatsoever. All Personal Information disclosed to Pfizer within a response will be utilized in accord with principles and polices as described at By submitting a response, you also acknowledge and confirm that you have consulted with your Technology Transfer Office, Business Development Office or any other required group and that you have their approval to submit the response. By submitting a response, you acknowledge that the Need's sponsoring organization, in its sole discretion, may select or reject a response or any portion thereof.


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Migrated from previous NineSights Community Site
Key success Criteria
Migrated from previous NineSights Community Site
Due Date
Apr 10, 2014
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Kevin Andrews
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