Accession Number : AD1033065


Title :   EphB1 as a Novel Drug Target to Combat Pain and Addiction


Descriptive Note : Technical Report,01 Sep 2015,31 Aug 2016


Corporate Author : University of Texas Southwestern Medical Center Dallas United States


Personal Author(s) : Henkemeyer,Mark


Full Text : http://www.dtic.mil/dtic/tr/fulltext/u2/1033065.pdf


Report Date : 01 Sep 2016


Pagination or Media Count : 10


Abstract : We have shown that the synaptic receptor protein known as EphB1 is a central player in nerve injury-induced neuropathic pain and the related pain symptoms associated with the withdrawal from opioid/morphine addiction. Our hypothesis is that postsynaptic EphB1 participates in pain through the ability of its extracellular domain to form protein-protein interactions with its presynaptic ligand, ephrin-B2, and the NR1 subunit of the postsynaptic NMDA receptor to inappropriately strengthen the synapses in the spinal cord that transmit pain signals into the brain. Our project is to carry out high-throughput screens (HTS) to identify small molecular weight drug-like compounds from a200,000 complex library that antagonize EphB1 protein-protein interactions. While we originally set out to target the EphB1:NR1 protein-protein interaction, we changed directions in Year 2 due to technical difficulties and are now focusing on the interaction of EphB1 with ephrin-B2. We have made good progress in developing HTS for antagonists that disrupt the EphB1:ephrin-B2 interaction and already have a small number of potential lead compounds from the initial pilot test screen of an 8,000 compound subset of the main library.


Descriptors :   drugs , pain , DRUG ADDICTION , receptor sites (physiology) , proteins , PAIN MANAGEMENT , wounds and injuries , ligands


Subject Categories : Medicine and Medical Research
      Pharmacology


Distribution Statement : APPROVED FOR PUBLIC RELEASE