Solvo Biotechnology

Advancell Diagnosztika Kft.

Solvo Biotechnológial Zrt.

Cellpharma Kft.

Termeszettudomanyi Kutatokozpont

Cellpharma LLC

Orbán, Tamás

Német, Katalin

Apáti, Ágota

Sarkadi, Balázs

Izsvák, Zsuzsanna

Creative Cell Kft.

Balázs Sarkadi

Ágnes Telbisz

Hristos Glavinas

Lajos Szente

Istvan Teplan

Janos Seprodi

Imre Mezo

Zsolt Vadasz

Borbala Vincze

Istvan Palyi

Gergely Szakács

Orsolya Csuka

Attila Németh

András Váradi

Szilvia Gedey

Várady György

László Homolya

Tamás Horváth

Nóra Kucsma

Dóra Kovács-türk

Edit Szabó

Maria Magocsi

György Várady

Ildikó Kasza

Dóra Méhn

Pál Ákos

Péter Krajcsi

Éva Fenyvesi

Raymond Evers

Éva Molnár

Tünde Nagy

Emese Kis

György Báthori

Csilla Özvegy

András Varadi

György Varadi

Olga Ujhelly

Ákos Pál

Ágota Apáti

Zsuzsanna Izsvák

Tamás Orbán

Katalin Német

Judit Cervenak

ABC multidrug transporters are key players in cancer multidrug resistance and in general xenobiotic elimination, thus their functional assays provide important tools for research and diagnostic applications. It has been found that in cells expressing functional ABCG2, ABCB1, or ABCC1 transporters, cellular PG fluorescence is strongly reduced. The invention relates to methods and uses of fluorescein derivative ester compounds of formula Ia which are analogs of PG for assessing ABC transporter activity of ABC multidrug transporters. The present accumulation assay is a novel tool for the parallel determination of the function of the multidrug transporters, in particular ABCG2, ABCB1, and ABCC1. The assay is applicable for diagnostic purposes and also allows the selection, separation and culturing of selected cell populations expressing such transporters.

Method of assessing ABC transporter activity using fluorescent dye accumulation assay

This invention relates to determination of quantitative expression of plasma membrane proteins as biomarkers in the erythrocytes. The invention includes simple, quantitative assay platforms which can be made available in most diagnostic laboratories. The platform allows performing personalized, quantitative tests for the direct expression level of a wide range of membrane proteins from small volume blood samples and connecting them to individual genetic variability, disease conditions, disease stages and complications, treatment protocols, pharmacological responses, or toxic side effects.

Quantitative determination of biomarkers in the erythrocyte membrane

The invention provides for a novel cholesterol loaded insect cell membrane preparation having an increased cholesterol level as compared to physiological cholesterol levels of insect cell membranes or to control insect cell membrane preparations without cholesterol loading, wherein said cholesterol loaded membrane preparation comprises an ABC transporter protein having an increased substrate transport activity due to increased cholesterol level of the membrane. The invention also relates to reagent kits comprising the preparations of the invention. The invention also relates to methods for manufacturing said preparations and methods for measuring any type of activity of the ABC transporters present in the cholesterol loaded membranes as well as studying or testing compounds and interaction of compounds and ABC transporters, in this assay systems. The invention also provides for a test system useful for testing whether ABC transporter proteins can be activated by cholesterol in an insect cell membrane.

Cholesterol loaded insect cell membranes as test proteins

The invention relates to a simple quantitative fluorescent assay method for determining the activity of transport proteins, more specifically multi-drug resistance associated proteins (MRPs). The method of the invention is performed on a well sealed culture of polarized cells expressing a transport protein of interest grown to confluency on a permeable support, said confluent cell culture forming well separated apical and basolateral compartments. The cells are contacted with a cell permeable non-fluorescent derivative of a fluorescent compound (e.g. calcein AM) in one compartment and, after a certain period of incubation, the fluorescence intensity detected in a sample taken from the opposite compartment is indicative of the activity of the transport protein of interest expressed in the cells. The invention also concerns methods for the qualitative and quantitative determination of inhibitors and activators of transport proteins of interest and methods for assessing basolateral and/or apical localization of plasma membrane bound transport proteins of interest in polarized cells.

Simple quantitative fluorescent assay method for determining the activity of transport proteins of interest

The invention features novel peptide derivatives called Reversins, and provides for their use in a method of reducing the activity of the multi-drug transporter protein MDR1 in order to overcome multidrug resistance in a mammal. The peptide derivatives are of the formula (I) X,-X,-X,(X,),-X,, wherein n is 0 or 1, and each n is the same or different; X,is BOC, BOC-Asu, Z-Asu, benzyloxycarbonyl, Glu(OBzl)-OBzl, Trp-OMe, Trp-Phe-OMe, Phe-Trp-OMe, Phe-Phe-OtBu, Trp-Trp-OtBu, indoloacetyl, benzoyl, an alkylanine of 1-4 carbons, dibenzylamide, tryptamide, 1-amino-adamantine, aminomethylcyclohexane, indoline, phenylethylamide or dicyclohexylamide; X,is Glu(OBzl), Asp(OBzl), succinyl, O,O-dibenzoyltartaroyl, diphenoyl, muconyl, Thx, Cpa, Asu, Nal, Pen, Phg, Dbt, Lys(BOC), Lys(Z), Cys(Bzl), Thr(Bzl), Glu(OtBu), tert.-Leu, Leu, Nle, Pro, Phe, Tyr(Bzl), or Ser(Bal); X,is Asp, Asu, Lys, Glu, Trp, Thx, Cpa, Nal, Pen, Phg, Dbt, Glu(OtBu), tert.-Leu, Leu, Nle, Pro, Tyr, Phe, or Tyr(Bzl); X,is BOC-Glu(OBzl), Glu(OBzl), Asu, OBzl, Bzl, BOC, BOC-Lys(BOC), Z-Glu(OtBu), Asp(OBzl), Asp(OBz)-OBzl, benzyloxycarbonyl, O-(cyclo-hexyl), fluorenylmethyl ester, Glu(OtBu), Glu(OtBu)-OBzl, 1-amino-adamantine, aminomethylcyclohexane, indoline, phenylethylarnide, or dicyclohexylamide; and X,is OMe, OBzl, OtBu, Phe-OMe, -O-(cyclohexyl), Trp-OMe, (chlorophenyl)-isobutylamide, fluorenylmethyl ester, ONp, 1-aminoadamantane, aminomethylcyclohexane, indoline, phenylethylamide, or dicyclohexylamide.

Compounds for reversing drug resistance

Growing community of inventors

Budapest, Hungary

Balázs Sarkadi