Összes szerző

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Kallai Judit

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 h_v1 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 (hH_V1) plays an important role in immune system and cancer cells being involved in functions such as proliferation, migration, and oxidative burst. H_V1 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 hH_V1 inhibitors. Currently, 5-chloro-2-guanidinobenzimidazole (ClGBI) is the most widely used inhibitor of H_V1 but it has low selectivity for the channel. This could lead to misinterpretation of functional assays addressing the role of H_V1 with the use of ClGBI. Thus, our aim was to find potent and more selective inhibitors for hH_V1, which could be useful research tools and serve as lead molecules for the development of drug molecules targeting H_V1.

We used patch-clamp to test the affinity and selectivity of potential inhibitors of H_V1 on CHO and HEK cells expressing hH_V1 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.