An Overview of Cell-Based Assay Platforms for the Solute Carrier Family of Transporters

Vojtech Dvorak; Tabea Wiedmer; Alvaro Ingles-Prieto; Patrick Altermatt; Helena Batoulis; Felix Bärenz; Eckhard Bender; Daniela Digles; Franz Dürrenberger; Laura H. Heitman; Adriaan P. IJzerman; Douglas B. Kell; Stefanie Kickinger; Daniel Körzö; Philipp Leippe; Thomas Licher; Vania Manolova; Riccardo Rizzetto; Francesca Sassone; Lia Scarabottolo; Avner Schlessinger; Vanessa Schneider; Hubert J. Sijben; Anna Lena Steck; Hanna Sundström; Sara Tremolada; Maria Wilhelm; Marina Wright Muelas; Diana Zindel; Claire M. Steppan; Giulio Superti-Furga

doi:10.3389/fphar.2021.722889

An Overview of Cell-Based Assay Platforms for the Solute Carrier Family of Transporters

Vojtech Dvorak
, Tabea Wiedmer
, Alvaro Ingles-Prieto
, Patrick Altermatt
, Helena Batoulis
, Felix Bärenz
, Eckhard Bender
, Daniela Digles
, Franz Dürrenberger
, Laura H. Heitman
, Adriaan P. IJzerman
, Douglas B. Kell
, Stefanie Kickinger
, Daniel Körzö
, Philipp Leippe
, Thomas Licher
, Vania Manolova
, Riccardo Rizzetto
, Francesca Sassone
, Lia Scarabottolo

Avner Schlessinger, Vanessa Schneider, Hubert J. Sijben, Anna Lena Steck, Hanna Sundström, Sara Tremolada, Maria Wilhelm, Marina Wright Muelas, Diana Zindel, Claire M. Steppan, Giulio Superti-Furga^*

^*Corresponding author for this work

Austrian Academy of Sciences
Vifor Pharma Management
Bayer AG
Aventis Pharma Germany GmbH
University of Vienna
Leiden University
Max Planck Institute for Medical Research
Axxam S.p.A.
Icahn School of Medicine at Mount Sinai
Pfizer Global R&D
University of Liverpool

Research output: Contribution to journal › Review › peer-review

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Abstract

The solute carrier (SLC) superfamily represents the biggest family of transporters with important roles in health and disease. Despite being attractive and druggable targets, the majority of SLCs remains understudied. One major hurdle in research on SLCs is the lack of tools, such as cell-based assays to investigate their biological role and for drug discovery. Another challenge is the disperse and anecdotal information on assay strategies that are suitable for SLCs. This review provides a comprehensive overview of state-of-the-art cellular assay technologies for SLC research and discusses relevant SLC characteristics enabling the choice of an optimal assay technology. The Innovative Medicines Initiative consortium RESOLUTE intends to accelerate research on SLCs by providing the scientific community with high-quality reagents, assay technologies and data sets, and to ultimately unlock SLCs for drug discovery.

Original language	English
Article number	722889
Journal	Frontiers in Pharmacology
Volume	12
Number of pages	31
ISSN	1663-9812
DOIs	https://doi.org/10.3389/fphar.2021.722889
Publication status	Published - 10 Aug 2021

Bibliographical note

Funding Information:
Assay technologies presented here are applied and developed further in the RESOLUTE consortium, a public-private partnership funded by the Innovative Medicines Initiative (IMI) of the European Union. RESOLUTE aims at empowering the research community with open-access reagents and data to unlock the SLC family for drug discovery. One of the main goals of RESOLUTE is to systematically assess the suitability of transport assay technologies for individual SLCs and develop them further (Superti-Furga et al., 2020). We are expecting to update this review with experience gained throughout the project.

Funding Information:
This work is part of the RESOLUTE project that has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement No. 777372. This Joint Undertaking receives support from the European Union’s

Publisher Copyright:
© Copyright © 2021 Dvorak, Wiedmer, Ingles-Prieto, Altermatt, Batoulis, Bärenz, Bender, Digles, Dürrenberger, Heitman, IJzerman, Kell, Kickinger, Körzö, Leippe, Licher, Manolova, Rizzetto, Sassone, Scarabottolo, Schlessinger, Schneider, Sijben, Steck, Sundström, Tremolada, Wilhelm, Wright Muelas, Zindel, Steppan and Superti-Furga.

Keywords

Cell-based assay
Chemical screening
Drug discovery
SLC
Solute carrier
Transporters

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Dvorak, V., Wiedmer, T., Ingles-Prieto, A., Altermatt, P., Batoulis, H., Bärenz, F., Bender, E., Digles, D., Dürrenberger, F., Heitman, L. H., IJzerman, A. P., Kell, D. B., Kickinger, S., Körzö, D., Leippe, P., Licher, T., Manolova, V., Rizzetto, R., Sassone, F., ... Superti-Furga, G. (2021). An Overview of Cell-Based Assay Platforms for the Solute Carrier Family of Transporters. Frontiers in Pharmacology, 12, Article 722889. https://doi.org/10.3389/fphar.2021.722889

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title = "An Overview of Cell-Based Assay Platforms for the Solute Carrier Family of Transporters",

abstract = "The solute carrier (SLC) superfamily represents the biggest family of transporters with important roles in health and disease. Despite being attractive and druggable targets, the majority of SLCs remains understudied. One major hurdle in research on SLCs is the lack of tools, such as cell-based assays to investigate their biological role and for drug discovery. Another challenge is the disperse and anecdotal information on assay strategies that are suitable for SLCs. This review provides a comprehensive overview of state-of-the-art cellular assay technologies for SLC research and discusses relevant SLC characteristics enabling the choice of an optimal assay technology. The Innovative Medicines Initiative consortium RESOLUTE intends to accelerate research on SLCs by providing the scientific community with high-quality reagents, assay technologies and data sets, and to ultimately unlock SLCs for drug discovery.",

keywords = "Cell-based assay, Chemical screening, Drug discovery, SLC, Solute carrier, Transporters",

author = "Vojtech Dvorak and Tabea Wiedmer and Alvaro Ingles-Prieto and Patrick Altermatt and Helena Batoulis and Felix B{\"a}renz and Eckhard Bender and Daniela Digles and Franz D{\"u}rrenberger and Heitman, \{Laura H.\} and IJzerman, \{Adriaan P.\} and Kell, \{Douglas B.\} and Stefanie Kickinger and Daniel K{\"o}rz{\"o} and Philipp Leippe and Thomas Licher and Vania Manolova and Riccardo Rizzetto and Francesca Sassone and Lia Scarabottolo and Avner Schlessinger and Vanessa Schneider and Sijben, \{Hubert J.\} and Steck, \{Anna Lena\} and Hanna Sundstr{\"o}m and Sara Tremolada and Maria Wilhelm and \{Wright Muelas\}, Marina and Diana Zindel and Steppan, \{Claire M.\} and Giulio Superti-Furga",

note = "Funding Information: Assay technologies presented here are applied and developed further in the RESOLUTE consortium, a public-private partnership funded by the Innovative Medicines Initiative (IMI) of the European Union. RESOLUTE aims at empowering the research community with open-access reagents and data to unlock the SLC family for drug discovery. One of the main goals of RESOLUTE is to systematically assess the suitability of transport assay technologies for individual SLCs and develop them further (Superti-Furga et al., 2020). We are expecting to update this review with experience gained throughout the project. Funding Information: This work is part of the RESOLUTE project that has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement No. 777372. This Joint Undertaking receives support from the European Union{\textquoteright}s Publisher Copyright: {\textcopyright} Copyright {\textcopyright} 2021 Dvorak, Wiedmer, Ingles-Prieto, Altermatt, Batoulis, B{\"a}renz, Bender, Digles, D{\"u}rrenberger, Heitman, IJzerman, Kell, Kickinger, K{\"o}rz{\"o}, Leippe, Licher, Manolova, Rizzetto, Sassone, Scarabottolo, Schlessinger, Schneider, Sijben, Steck, Sundstr{\"o}m, Tremolada, Wilhelm, Wright Muelas, Zindel, Steppan and Superti-Furga.",

year = "2021",

month = aug,

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doi = "10.3389/fphar.2021.722889",

language = "English",

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Dvorak, V, Wiedmer, T, Ingles-Prieto, A, Altermatt, P, Batoulis, H, Bärenz, F, Bender, E, Digles, D, Dürrenberger, F, Heitman, LH, IJzerman, AP, Kell, DB, Kickinger, S, Körzö, D, Leippe, P, Licher, T, Manolova, V, Rizzetto, R, Sassone, F, Scarabottolo, L, Schlessinger, A, Schneider, V, Sijben, HJ, Steck, AL, Sundström, H, Tremolada, S, Wilhelm, M, Wright Muelas, M, Zindel, D, Steppan, CM & Superti-Furga, G 2021, 'An Overview of Cell-Based Assay Platforms for the Solute Carrier Family of Transporters', Frontiers in Pharmacology, vol. 12, 722889. https://doi.org/10.3389/fphar.2021.722889

TY - JOUR

T1 - An Overview of Cell-Based Assay Platforms for the Solute Carrier Family of Transporters

AU - Dvorak, Vojtech

AU - Wiedmer, Tabea

AU - Ingles-Prieto, Alvaro

AU - Altermatt, Patrick

AU - Batoulis, Helena

AU - Bärenz, Felix

AU - Bender, Eckhard

AU - Digles, Daniela

AU - Dürrenberger, Franz

AU - Heitman, Laura H.

AU - IJzerman, Adriaan P.

AU - Kell, Douglas B.

AU - Kickinger, Stefanie

AU - Körzö, Daniel

AU - Leippe, Philipp

AU - Licher, Thomas

AU - Manolova, Vania

AU - Rizzetto, Riccardo

AU - Sassone, Francesca

AU - Scarabottolo, Lia

AU - Schlessinger, Avner

AU - Schneider, Vanessa

AU - Sijben, Hubert J.

AU - Steck, Anna Lena

AU - Sundström, Hanna

AU - Tremolada, Sara

AU - Wilhelm, Maria

AU - Wright Muelas, Marina

AU - Zindel, Diana

AU - Steppan, Claire M.

AU - Superti-Furga, Giulio

N1 - Funding Information: Assay technologies presented here are applied and developed further in the RESOLUTE consortium, a public-private partnership funded by the Innovative Medicines Initiative (IMI) of the European Union. RESOLUTE aims at empowering the research community with open-access reagents and data to unlock the SLC family for drug discovery. One of the main goals of RESOLUTE is to systematically assess the suitability of transport assay technologies for individual SLCs and develop them further (Superti-Furga et al., 2020). We are expecting to update this review with experience gained throughout the project. Funding Information: This work is part of the RESOLUTE project that has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under Grant Agreement No. 777372. This Joint Undertaking receives support from the European Union’s Publisher Copyright: © Copyright © 2021 Dvorak, Wiedmer, Ingles-Prieto, Altermatt, Batoulis, Bärenz, Bender, Digles, Dürrenberger, Heitman, IJzerman, Kell, Kickinger, Körzö, Leippe, Licher, Manolova, Rizzetto, Sassone, Scarabottolo, Schlessinger, Schneider, Sijben, Steck, Sundström, Tremolada, Wilhelm, Wright Muelas, Zindel, Steppan and Superti-Furga.

PY - 2021/8/10

Y1 - 2021/8/10

N2 - The solute carrier (SLC) superfamily represents the biggest family of transporters with important roles in health and disease. Despite being attractive and druggable targets, the majority of SLCs remains understudied. One major hurdle in research on SLCs is the lack of tools, such as cell-based assays to investigate their biological role and for drug discovery. Another challenge is the disperse and anecdotal information on assay strategies that are suitable for SLCs. This review provides a comprehensive overview of state-of-the-art cellular assay technologies for SLC research and discusses relevant SLC characteristics enabling the choice of an optimal assay technology. The Innovative Medicines Initiative consortium RESOLUTE intends to accelerate research on SLCs by providing the scientific community with high-quality reagents, assay technologies and data sets, and to ultimately unlock SLCs for drug discovery.

AB - The solute carrier (SLC) superfamily represents the biggest family of transporters with important roles in health and disease. Despite being attractive and druggable targets, the majority of SLCs remains understudied. One major hurdle in research on SLCs is the lack of tools, such as cell-based assays to investigate their biological role and for drug discovery. Another challenge is the disperse and anecdotal information on assay strategies that are suitable for SLCs. This review provides a comprehensive overview of state-of-the-art cellular assay technologies for SLC research and discusses relevant SLC characteristics enabling the choice of an optimal assay technology. The Innovative Medicines Initiative consortium RESOLUTE intends to accelerate research on SLCs by providing the scientific community with high-quality reagents, assay technologies and data sets, and to ultimately unlock SLCs for drug discovery.

KW - Cell-based assay

KW - Chemical screening

KW - Drug discovery

KW - SLC

KW - Solute carrier

KW - Transporters

U2 - 10.3389/fphar.2021.722889

DO - 10.3389/fphar.2021.722889

M3 - Review

C2 - 34447313

AN - SCOPUS:85113406662

SN - 1663-9812

VL - 12

JO - Frontiers in Pharmacology

JF - Frontiers in Pharmacology

M1 - 722889

ER -

An Overview of Cell-Based Assay Platforms for the Solute Carrier Family of Transporters

Abstract

Bibliographical note

Keywords

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