Cel Voltage gated sodium channels (NaVs) are the primary transmembrane proteins underlying fast electrical communication in neurons of the peripheral and central nervous system (PNS and CNS). Being such an integral part of neuronal signaling, they are implicated in a number of severe diseases that have a major impact on human society. However, drugs and established therapies targeting NaVs are rare due to common off-target effects. Therefore, new NaV-blockers will be developed and used for in vivo imaging using positron emission tomography (PET). For this purpose, novel derivatives of the recently disclosed truncated batrachotoxin (tr-BTX), which represent a completely new type of NaV-blockers, will be synthesized and their ability to block different NaV isoforms (NaV1.1 to 1.8) will be tested using fluorescent assays. The most promising candidates will then be labeled using different positron emitting isotopes such as carbon-11 (11C) and fluorine-18 (18F) exploiting different radioactive half-lifes and metabolic stability. The resulting “hot-tr-BTX” will be subsequently employed in small rodent PET-scans revealing their in vivo pharmacokinetics. This novel and unique tool will provide three major immediate benefits. First, hot-tr-BTX might deliver a general imaging probe for nervous activity in the PNS, and potentially the CNS, by monitoring NaV function in vivo. Secondly, this will allow the investigation of various pain conditions and neurodegenerative diseases and link their pathogenesis to NaV-function. Thirdly, the proposed research might deliver not only new NaV-blockers as potential drug candidates, but will also provide a valuable method facilitating the development of long awaited drugs targeting NaVs for pain therapy, a goal that is currently intensely investigated by numerous European and global pharmaceutical companies. Dziedzina nauki natural sciencesbiological sciencesneurobiologymedical and health sciencesbasic medicinepharmacology and pharmacydrug discoverynatural scienceschemical sciencesinorganic chemistryalkali metalsnatural sciencesbiological sciencesbiochemistrybiomoleculesproteinsmedical and health sciencesbasic medicinepharmacology and pharmacypharmacokinetics Słowa kluczowe Voltage Gated Sodium Channels Pain Research Neurodegeneratie Diseases Modified Natural Products Medicinal Chemistry Positron Emission Tomography Program(-y) H2020-EU.1.3. - EXCELLENT SCIENCE - Marie Skłodowska-Curie Actions Main Programme H2020-EU.1.3.2. - Nurturing excellence by means of cross-border and cross-sector mobility Temat(-y) MSCA-IF-2014-GF - Marie Skłodowska-Curie Individual Fellowships (IF-GF) Zaproszenie do składania wniosków H2020-MSCA-IF-2014 Zobacz inne projekty w ramach tego zaproszenia System finansowania MSCA-IF - Marie Skłodowska-Curie Individual Fellowships (IF) Koordynator KLINIKUM DER UNIVERSITAET ZU KOELN Wkład UE netto € 239 860,80 Adres Kerpener Strasse 62 50937 Koeln Niemcy Zobacz na mapie Region Nordrhein-Westfalen Köln Köln, Kreisfreie Stadt Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 239 860,80 Partnerzy (1) Sortuj alfabetycznie Sortuj według wkładu UE netto Rozwiń wszystko Zwiń wszystko Partner Organizacje partnerskie biorą udział w realizacji działania, jednak nie podpisują umowy o grant. BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY Stany Zjednoczone Wkład UE netto € 0,00 Adres SERRA MALL 450 94305 2004 Stanford Zobacz na mapie Rodzaj działalności Higher or Secondary Education Establishments Linki Kontakt z organizacją Opens in new window Strona internetowa Opens in new window Uczestnictwo w unijnych programach w zakresie badań i innowacji Opens in new window sieć współpracy HORIZON Opens in new window Koszt całkowity € 160 130,40
