Core Facility

Jens Peter von Kries

Screening Unit

Portrait

The Screening Unit provides an open access high throughput technology platform for screening compound libraries (170.000 drug like compounds) and for genome-wide RNA-interference or CRISPR-Cas9 gene-editing (human and mouse) using automated microscopes and a broad panel of other devices (see >Technologies).


Open Access Plattform

Project Application

Contact us via E-Mail: --> see Contact

For effective support and data documentation you need to fill in the requested information                                                           and send us the project application form

 

For screening of the FMP in-house small molecule library:

Project application form for screening the FMP library

 

For screening of the EU-OPENSCREEN ECBL library:

Project application form for screening the EU-OS library

Information about EU-OPENSCREEN

 

Assay Setup
You may visit the Screening Unit, where we can help you in assay transfer to the 384well format and test your assay set up together for HTS usage. You will then be able to update the project application form with the revised protocol. Afterwards the material & reagent costs for your next visit and primary screen plus validation are calculated.

Primary Screen
We perform the primary screen together with one person from your team, the data are documented and analyzed automatically. You receive the raw data, statistic analysis, and statistics-based hit lists containing also structural data.

Review of hit lists
If desired, you may revise the hit lists. You send us a list of 352 compounds via e-mail.

Cherry picking
We provide you with a 384-well plate containing your requested 352 hits, (4 µl 5mM compound in DMSO).

Quality control of 352 hit compounds via LC-MS Analysis
A small aliquot (0.2 µl) of your hit picking plate is taken and diluted in ACN/H2O for the LC-MS analysis. We analyze the samples in ACN/H2O (1:1, 25 µM) with our Agilent TOF mass spectrometer and determine the purity via UV absorption at 254 nm.

IC50 validation
IC50 validation (using nine serial dilutions of the compounds in duplicate) is carried out by us, the data are analyzed automatically. You receive for a maximum of 352 "hit" compounds IC50 reports containing MS analysis data, frequent hitter information, data from biophysical and cytotox profiling. To our experience less then 10% of the compounds from the hit list of 352 can be expected to be true hits.

Review of IC50 data
Our chemists revise with you the list of validated compounds and suggest proposals, which compounds might be selected for further characterization and optimization of leads.
Please bear in mind that all steps need only to be performed once per project!

The Screening Unit can assist your project with know-how gained from about 170 previous screens. But the data documentation, analysis and follow up studies are in the responsibility of the PI of the project.

RNAi and CRISPR-based Screening

The facility offers scientists from the FMP and MDC access to high-throughput screening with arrayed miRNA, siRNA and sgRNA libraries on the basis of a scientific collaboration.

Broad range of assays
State of the art equipment supports a broad range of assays in high-throughput formats, ranging from basic reporter assays to high-content screening campaigns. Instrumentation covers automated fluorescence microscopy, flow cytometry, luminescence and real-time kinetic fluorescence reading (see Technologies).

Full support in high-throughput screening
We operate on the basis of a scientific collaboration and offer support through all stages of a screening campaign: assay development and adaption to high-throughput screening, the actual wet-lab screen, data acquisition and quality assessment, statistical analysis as well as hit candidate selection.

Data processing
We are constantly advancing our in-house analysis, database and reporting tools to keep the platform updated. The integration of freely available open-source tools (e.g. KNIME Analytics Platform) and the development of our own analysis workflows enables us to meet the specific requirements of a multitude of biological questions.

Tools for Assay Setup

Contact Office

Dajana Baudach

Secretary, Sun Group,
Secretary Nazaré Group


Research Section

Chemical Biology

Publications via ORCID

Structure-Based Design of Xanthine-Imidazopyridines and -Imidazothiazoles as Highly Potent and In Vivo Efficacious Tryptophan Hydroxylase Inhibitors.

  • Specker E; Wesolowski R; Schütz A; Matthes S; Mallow K; Wasinska-Kalwa M; Winkler L; Oder A; Alenina N; Pleimes D; von Kries JP; Heinemann U; Bader M; Nazaré M

Journal of medicinal chemistry 2023

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Discovery of tetrazolo-pyridazine-based small molecules as inhibitors of MACC1-driven cancer metastasis.

  • Yan S; Schöpe PC; Lewis J; Putzker K; Uhrig U; Specker E; von Kries JP; Lindemann P; Omran A; Sanchez-Ibarra HE; Unger A; Zischinsky ML; Klebl B; Stein U

Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 2023

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An unconventional gatekeeper mutation sensitizes inositol hexakisphosphate kinases to an allosteric inhibitor.

  • Aguirre T; Dornan GL; Hostachy S; Neuenschwander M; Seyffarth C; Haucke V; Schütz A; von Kries JP; Fiedler D

eLife 2023

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Small Molecules Targeting Human UDP-GlcNAc 2-Epimerase.

  • Gorenflos López JL; Dornan GL; Boback N; Neuenschwander M; Oder A; Kemnitz-Hassanin K; Schmieder P; Specker E; Asikoglu HC; Oberdanner C; Hackenberger CPR

Chembiochem : a European journal of chemical biology 2023

read online

Structural Basis for Highly Selective Class II Alpha Phosphoinositide-3-Kinase Inhibition.

  • Kücükdisli M; Bel-Abed H; Cirillo D; Lo WT; Efrém NL; Horatscheck A; Perepelittchenko L; Prokofeva P; Ehret TAL; Radetzki S; Neuenschwander M; Nazaré M

Journal of medicinal chemistry 2023

read online

7,8-Dihydroxyflavone is a direct inhibitor of pyridoxal phosphatase

  • Zink C; Witzinger L; Keller A; Hadamek K; Bothe S; Neuenschwander M; Villmann C; von Kries JP; Schindelin H; Jeanclos E; Gohla A
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Role of endothelial cells and angiotensin converting enzyme-II in COVID-19 and brain damages post-infection.

  • Mehboob R; von Kries JP; Ehsan K; Almansouri M; Bamaga AK

Frontiers in neurology 2023

read online

An unconventional gatekeeper mutation sensitizes inositol hexakisphosphate kinases to an allosteric inhibitor

  • Aguirre T; Dornan GL; Hostachy S; Neuenschwander M; Seyffarth C; Haucke V; Schütz A; von Kries JP; Fiedler D
read online

Large-scale microRNA functional high-throughput screening identifies miR-515-3p and miR-519e-3p as inducers of human cardiomyocyte proliferation.

  • Renikunta HV; Lazarow K; Gong Y; Shukla PC; Nageswaran V; Giral H; Kratzer A; Opitz L; Engel FB; Haghikia A; Costantino S; Paneni F; von Kries JP; Jakob P

iScience 2023

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Small molecule inhibiting microglial nitric oxide release could become a potential treatment for neuroinflammation.

  • Jordan P; Costa A; Specker E; Popp O; Volkamer A; Piske R; Obrusnik T; Kleissle S; Stuke K; Rex A; Neuenschwander M; von Kries JP; Nazare M; Wolf SA

PloS one 2023

read online

The FGFR inhibitor PD173074 binds to the C-terminus of oncofetal HMGA2 and modulates its DNA-binding and transcriptional activation functions.

  • Ahmed SM; Ragunathan P; Shin J; Peter S; Kleissle S; Neuenschwander M; Schäfer R; Kries JPV; Grüber G; Dröge P

FEBS letters 2023

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Glycolytic flux control by drugging phosphoglycolate phosphatase.

  • Jeanclos E; Schlötzer J; Hadamek K; Yuan-Chen N; Alwahsh M; Hollmann R; Fratz S; Yesilyurt-Gerhards D; Frankenbach T; Engelmann D; Keller A; Gohla A

Nature communications 2022

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TSG101 associates with PARP1 and is essential for PARylation and DNA damage-induced NF-κB activation.

  • Tufan AB; Lazarow K; Kolesnichenko M; Sporbert A; von Kries JP; Scheidereit C

The EMBO journal 2022

read online

Development of selective inhibitors of phosphatidylinositol 3-kinase C2α.

  • Lo WT; Belabed H; Kücükdisli M; Metag J; Roske Y; Prokofeva P; Ohashi Y; Horatscheck A; Cirillo D; Krauss M; Schmied C; Neuenschwander M; Haucke V

Nature chemical biology 2022

read online

Structure-Based Design of Xanthine-Benzimidazole Derivatives as Novel and Potent Tryptophan Hydroxylase Inhibitors.

  • Specker E; Matthes S; Wesolowski R; Schütz A; Grohmann M; Alenina N; Pleimes D; Mallow K; Neuenschwander M; Gogolin A; Weise M; Pfeifer J; Ziebart N; Bader M

Journal of medicinal chemistry 2022

read online

Disruptors of AKAP-Dependent Protein-Protein Interactions.

  • Walker-Gray R; Pallien T; Miller DC; Oder A; Neuenschwander M; von Kries JP; Diecke S; Klussmann E

Methods in molecular biology (Clifton, N.J.) 2022

read online

Aurora Kinase A Is Involved in Controlling the Localization of Aquaporin-2 in Renal Principal Cells

  • Sandrine Baltzer; Timur Bulatov; Christopher Schmied; Andreas Krämer; Benedict-Tilman Berger; Andreas Oder; Ryan Walker-Gray; Christin Kuschke; Kerstin Zühlke; Jenny Eichhorst; Martin Lehmann; Stefan Knapp; John Weston; Jens Von Kries; Roderich D. Süssmuth; Enno Klussmann

International Journal of Molecular Sciences 2022

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A New Highly Thyrotropin Receptor-Selective Small-Molecule Antagonist with Potential for the Treatment of Graves' Orbitopathy.

  • Marcinkowski P; Hoyer I; Specker E; Furkert J; Rutz C; Neuenschwander M; Sobottka S; Sun H; Nazare M; Berchner-Pfannschmidt U; von Kries JP; Krause G

Thyroid : official journal of the American Thyroid Association 2018

read online

Use of a sequential high throughput screening assay to identify novel inhibitors of the eukaryotic SRP-Sec61 targeting/translocation pathway.

  • Klein W; Rutz C; Eckhard J; Provinciael B; Specker E; Neuenschwander M; Kleinau G; Scheerer P; von Kries JP; Nazaré M; Vermeire K; Schülein R

PloS one 2018

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Systematic pharmacological screens uncover novel pathways involved in cerebral cavernous malformations.

  • Otten C; Knox J; Boulday G; Eymery M; Haniszewski M; Neuenschwander M; Radetzki S; Vogt I; Hähn K; De Luca C; Cardoso C; Hamad S; Igual Gil C; Roy P; Abdelilah-Seyfried S

EMBO molecular medicine 2018

read online

Drug discovery with an RBM20 dependent titin splice reporter identifies cardenolides as lead structures to improve cardiac filling.

  • Liss M; Radke MH; Eckhard J; Neuenschwander M; Dauksaite V; von Kries JP; Gotthardt M

PloS one 2018

read online

Loss-of-function uORF mutations in human malignancies.

  • Schulz J; Mah N; Neuenschwander M; Kischka T; Ratei R; Schlag PM; Castaños-Vélez E; Fichtner I; Tunn PU; Denkert C; Klaas O; Berdel WE; von Kries JP; Wethmar K

Scientific reports 2018

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An AKAP-Lbc-RhoA interaction inhibitor promotes the translocation of aquaporin-2 to the plasma membrane of renal collecting duct principal cells.

  • Schrade K; Tröger J; Eldahshan A; Zühlke K; Abdul Azeez KR; Elkins JM; Neuenschwander M; Oder A; Elkewedi M; Jaksch S; Andrae K; Li J; Fernandes J; Klussmann E

PloS one 2018

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Small Molecules Targeting Human N-Acetylmannosamine Kinase.

  • Hinderlich S; Neuenschwander M; Wratil PR; Oder A; Lisurek M; Nguyen LD; von Kries JP; Hackenberger CPR

Chembiochem : a European journal of chemical biology 2017

read online

Discovery of a Novel Series of Tankyrase Inhibitors by a Hybridization Approach.

  • Anumala UR; Waaler J; Nkizinkiko Y; Ignatev A; Lazarow K; Lindemann P; Olsen PA; Murthy S; Obaji E; Majouga AG; Leonov S; von Kries JP; Lehtiö L; Nazaré M

Journal of medicinal chemistry 2017

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A Chemical Disruptor of the ClpX Chaperone Complex Attenuates the Virulence of Multidrug-Resistant Staphylococcus aureus.

  • Fetzer C; Korotkov VS; Thänert R; Lee KM; Neuenschwander M; von Kries JP; Medina E; Sieber SA

Angewandte Chemie (International ed. in English) 2017

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Neuronal Chemosensation and Osmotic Stress Response Converge in the Regulation of <i>aqp-8</i> in <i>C. elegans</i>.

  • Igual Gil C; Jarius M; von Kries JP; Rohlfing AK

Frontiers in physiology 2017

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Statin and rottlerin small-molecule inhibitors restrict colon cancer progression and metastasis via MACC1.

  • Juneja M; Kobelt D; Walther W; Voss C; Smith J; Specker E; Neuenschwander M; Gohlke BO; Dahlmann M; Radetzki S; Preissner R; von Kries JP; Schlag PM; Stein U

PLoS biology 2017

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Identification of a Novel Benzimidazole Pyrazolone Scaffold That Inhibits KDM4 Lysine Demethylases and Reduces Proliferation of Prostate Cancer Cells.

  • Carter DM; Specker E; Przygodda J; Neuenschwander M; von Kries JP; Heinemann U; Nazaré M; Gohlke U

SLAS discovery : advancing life sciences R & D 2017

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