Összes szerző


Feher Adam

az alábbi absztraktok szerzői között szerepel:

Domingos Geraldo Jorge
Identification of inhibitors of the human hv1 proton channel

Aug 30 - szerda

15:30 – 17:00

II. Poszterszekció

P40

Identification of inhibitors of the human hv1 proton channel

Geraldo Domingos1, Adam Feher1, Eva Korpos 1,2, Tibor G. Szanto1, Martina Piga3, Tihomir Tomasic3, Nace Zidar3, Adrienn Gyongyosi4, Judit Kallai4, Arpad Lanyi4, Ferenc Papp1, Katinka Gyuris1, Zoltan Varga1

1 Department of Biophysics and Cell Biology, Faculty of Medicine, University of Debrecen, Hungary,

2 MTA-DE Cell Biology and Signalling Research Group, Faculty of Medicine, University of Debrecen, Hungary

3 Department of Pharmaceutical Chemistry, University of Ljubljana, Slovenia, 4 Department of Immunology, Faculty of Medicine, University of Debrecen, Hungary

The human voltage-gated proton channel (hHV1) plays an important role in immune system and cancer cells being involved in functions such as proliferation, migration, and oxidative burst. HV1 does not have a conventional ion-conducting pore, the conduction occurs through the voltage-sensing domain. This difference may be the reason for the lack of selective hHV1 inhibitors. Currently, 5-chloro-2-guanidinobenzimidazole (ClGBI) is the most widely used inhibitor of HV1 but it has low selectivity for the channel. This could lead to misinterpretation of functional assays addressing the role of HV1 with the use of ClGBI. Thus, our aim was to find potent and more selective inhibitors for hHV1, which could be useful research tools and serve as lead molecules for the development of drug molecules targeting HV1.

We used patch-clamp to test the affinity and selectivity of potential inhibitors of HV1 on CHO and HEK cells expressing hHV1 and other channels. Seven “hit” molecules were identified among the NZ family of compounds of which NZ-13 has the best selectivity profile.

The widely-used HV1 inhibitor ClGBI blocks various ion channels and therefore is not a selective HV1 blocker. This must be considered in functional tests investigating the role of HV1 in healthy and pathological conditions.

We have identified a new family of hHV1 inhibitors, which have comparable affinities for the channel to ClGBI.

Most NZ molecules have low selectivity for hHV1, but NZ-13, the one with the highest selectivity, may be better suited for functional tests than ClGBI as it inhibits T cell proliferation less.