Core Facility

Edgar Specker

Compound Management

portrait edgar specker

The aim of the Core Facility Compound Mangement is the production of screening plates for the primary screening at the Screening Unit, the preparation of hitpicking plates in order to conduct concentration-dependent validations of primary hits, the QC-controls of these hits and the support of users to prioritize their hit lists.


Profile

The goal of the core facility is the provision of screening plates to the Screening Unit and the preparation of hitpicking plates to conduct concentration-dependent validations of hits. It performs the QC-controls and helps the user to prioritize the hit lists. It manages a  library of 80.000 compounds, including a commercial library of 40.000 compounds, an academic library of 10.000 compounds and 30.000 natural product derived compounds.

 

About the Facility

The Compound Management was initiated in 2010 to facilitate the access for the academic community to a state-of-the-art compound management facility and was upgraded over the last decade. Initially, it started as an integral part of the Screening Unit and the Medicinal Chemistry group before it became an independent Core Faciltiy in 01/2020. At first, a REMP storage system hosted a compound library of 37.000 compound. Due to the higher demand of the constantly growing commercial and academic libraries an upgrade to the automated KIWI storage system was required with a larger capacity of 110.000 compounds. Today, it manages a highly diverse library of 80.000 compounds including a fragment and bioactive library of different commercial vendors. Over the years a academic library of about 10.000 compounds was collected from a huge variety of academic chemistry groups together with 30.000 natural product derived compounds from Analyticon Discovery GmbH. In 2019, it moved next to the laboratories of the EU-OPENSCREEN ERIC where both infrastructures will benefit from each other using theirs synergies while maintaining their different strategic and scientific operations. The ultimate goals of the Core Facility is the provision of screening plates for the primary screening at the Screening Unit, the preparation of hitpicking plates in order to conduct concentration-dependent validations of primary hits, the QC-controls of these hits and the support of users to prioritize their hit lists. 

Group Leader

Compound Management

The Compound Management manages the central compound collection of the FMP using a Liconic-KIWI storage systems combined with a FreedomEvo pipetting system (Tecan).  The collection is extended by donations of academic chemists, 4000 biology-annotated compounds (Selleck library) and a natural product collection of 20.000 cpds from AnalytiCon Discovery which assembles a smart library collections of 75.000 compounds ready to screen. The automated storage system provides a capacity of about 110.000 cpds with a total number of 220.000 tubes stored at -20° C. The Compound Management actively collects compound collections from academic chemists and currently holds about 8.000 unique donated cpds.
The collection of commercially available compounds has been financed by the FMP in cooperation with the Max-Delbrück-Centrum für Molekulare Medizin Berlin-Buch (MDC), the Helmholtz-Zentrum für Infektionsforschung (HZI), and the University of Konstanz. The design and selection of compounds is based on a maximum common substructure analysis of the World Drug Index (WDI).
The project-oriented chemical synthesis and optimization of small molecules is supported by medicinal chemists, drug modellers and structural biologists at the Institute on the basis of individual cooperations.

KIWI Store (220.000 tubes)

The KIWI Store (LiCONiC AG) offer fully automated storage and retrieval of compounds with a total number of 220.000 tubes organized in 96-tube racks. The tubes contain 200 µl DMSO solutions for each compound at concentrations of 10 mM in DMSO. Individual tubes are identified by a 2D-barcode at bottom and the racks by 1D-barcodes. The provided technology enables individual sample access and manipulation by simply pushing the tube through the source rack to an empty destination rack.The automated selection of individual tubes in the -20°C freezer also o ffers the benefits of minimizing freeze/thaw cycles, library cleaning and compression, and avoiding oxidation and water uptake. This is especially important for the unique compounds donated from academic chemists and protects the long term storage. Furthermore this technology enables  for generation of target specific sub libraries .The software tracks the samples at all stages and allows them to be chosen for retrieval from imported sample lists or queries. After samples are picked in the -20 °C environment they are delivered in delivery racks for further processing. The delivery rack is returned to the KIWI Store and the software automatically updates the location of the rack inside the store. 

Dr. Martin Neuenschwander (Screening Unit) has programmed a visual basic script allowing the communication between the relational database of the KIWI Store and the file-based system of the Freedom EVO liquid handling workstation, creating a fully automated liquid handling and sample management platform. 
The task of hit picking from 96 tube racks to reformat to the 384 screening plates runs on a routine basis. Furthermore work lists for desolvation of solid compounds in glass vials automatically drive the liquid handling module to transfer the calculated DMSO volumes in order to create a 10 mM concentration. Later, the solution in transferred to 96 tube racks and deliveres in a automated fashion to the KIWI Store.

Über die Technologieplattform

The Compound Management was initiated in 2010 to facilitate the access for the academic community to a state-of-the-art compound management facility and was upgraded over the last decade. Initially, it started as an integral part of the Screening Unit and the Medicinal Chemistry group before it became an independent Core Faciltiy in 01/2020. At first, a REMP storage system hosted a compound library of 37.000 compound. Due to the higher demand of the constantly growing commercial and academic libraries an upgrade to the automated KIWI storage system was required with a larger capacity of 110.000 compounds. Today, it manages a diversity library of 43.000 compounds and a fragment library of 4000 compounds purchased from different commercial vendors. Over the years a academic library of about 8000 compounds was collected from a huge variety of academic chemistry groups together with 20.000 natural product derived compounds from Analyticon Discovery GmbH. In 2019, it moved next to the laboratories of the EU-OPENSCREEN ERIC where both infrastructures will benefit from each other using theirs synergies while maintaining their different strategic and scientific operations. The ultimate goals of the Core Facility is the provision of screening plates for the primary screening at the Screening Unit, the preparation of hitpicking plates in order to conduct concentration-dependent validations of primary hits, the QC-controls of these hits and the support of users to prioritize their hit lists. 

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

  • Edgar Specker; Radoslaw Wesolowski; Anja Schütz; Susann Matthes; Keven Mallow; Malgorzata Wasinska-Kalwa; Lars Winkler; Andreas Oder; Natalia Alenina; Dirk Pleimes; Jens Peter von Kries; Udo Heinemann; Michael Bader; Marc Nazaré

Journal of Medicinal Chemistry 2023

read online

Small Molecules Targeting Human UDP‐GlcNAc 2‐Epimerase

  • Jacob L. Gorenflos López; Gillian L. Dornan; Nico Boback; Martin Neuenschwander; Andreas Oder; Kristin Kemnitz‐Hassanin; Peter Schmieder; Edgar Specker; Hatice Ceyda Asikoglu; Christian Oberdanner; Carola Seyffarth; Jens Peter von Kries; Daniel Lauster; Stephan Hinderlich; Christian P.R. Hackenberger

ChemBioChem 2023

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

  • Philipp Jordan; Amanda Costa; Edgar Specker; Oliver Popp; Andrea Volkamer; Regina Piske; Tessa Obrusnik; Sabrina Kleissle; Kevin Stuke; André Rex; Martin Neuenschwander; Jens Peter von Kries; Marc Nazare; Phillip Mertins; Helmut Kettenmann; Susanne A. Wolf

PLOS ONE 2023

read online

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

  • Shixian Yan; Paul Curtis Schöpe; Joe Lewis; Kerstin Putzker; Ulrike Uhrig; Edgar Specker; Jens Peter von Kries; Peter Lindemann; Anahid Omran; Hector E. Sanchez-Ibarra; Anke Unger; Mia-Lisa Zischinsky; Bert Klebl; Wolfgang Walther; Marc Nazaré; Dennis Kobelt; Ulrike Stein

Biomedicine & Pharmacotherapy 2023

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

  • Murat Kücükdisli; Hassen Bel-Abed; Davide Cirillo; Wen-Ting Lo; Nina-Louisa Efrém; André Horatscheck; Liudmila Perepelittchenko; Polina Prokofeva; Theresa A. L. Ehret; Silke Radetzki; Martin Neuenschwander; Edgar Specker; Guillaume Médard; Susanne Müller; Stephanie Wilhelm; Bernhard Kuster; Jens Peter von Kries; Volker Haucke; Marc Nazare

Journal of Medicinal Chemistry 2023

read online
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Small-Molecule Lysophosphatidic Acid Receptor 5 (LPAR5) Antagonists: Versatile Pharmacological Tools to Regulate Inflammatory Signaling in BV-2 Microglia Cells

  • Ioanna Plastira; Lisha Joshi; Eva Bernhart; Jens Schoene; Edgar Specker; Marc Nazare; Wolfgang Sattler

Frontiers in Cellular Neuroscience 2019

read online

EU-OPENSCREEN: A Novel Collaborative Approach to Facilitate Chemical Biology

  • Philip Brennecke; Dace Rasina; Oscar Aubi; Katja Herzog; Johannes Landskron; Bastien Cautain; Francisca Vicente; Jordi Quintana; Jordi Mestres; Bahne Stechmann; Bernhard Ellinger; Jose Brea; Jacek L. Kolanowski; Radosław Pilarski; Mar Orzaez; Antonio Pineda-Lucena; Luca Laraia; Faranak Nami; Piotr Zielenkiewicz; Kamil Paruch; Espen Holst Hansen; Jens P. von Kries; Martin Neuenschwander; Edgar Specker; Petr Bartunek; Sarka Simova; Zbigniew Leśnikowski; Stefan Krauss; Lari Lehtiö; Ursula Bilitewski; Mark Brönstrup; Kjetil Taskén; Aigars Jirgensons; Heiko Lickert; Mads H. Clausen; Jeanette H. Andersen; Maria J. Vicent; Olga Genilloud; Aurora Martinez; Marc Nazaré; Wolfgang Fecke; Philip Gribbon

SLAS Discovery 2019

read online

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

  • Patrick Marcinkowski; Inna Hoyer; Edgar Specker; Jens Furkert; Claudia Rutz; Martin Neuenschwander; Sebastian Sobottka; Han Sun; Marc Nazare; Utta Berchner-Pfannschmidt; Jens Peter von Kries; Anja Eckstein; Ralf Schülein; Gerd Krause

Thyroid 2019

read online

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

  • David M. Carter; Edgar Specker; Jessica Przygodda; Martin Neuenschwander; Jens Peter von Kries; Udo Heinemann; Marc Nazaré; Ulrich Gohlke

SLAS Discovery 2017

read online

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

  • Manisha Juneja; Dennis Kobelt; Wolfgang Walther; Cynthia Voss; Janice Smith; Edgar Specker; Martin Neuenschwander; Björn-Oliver Gohlke; Mathias Dahlmann; Silke Radetzki; Robert Preissner; Jens Peter von Kries; Peter Michael Schlag; Ulrike Stein

PLOS Biology 2017

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Small-molecule inhibition of STOML3 oligomerization reverses pathological mechanical hypersensitivity

  • Christiane Wetzel; Simone Pifferi; Cristina Picci; Caglar Gök; Diana Hoffmann; Bali KK; André Lampe; Liudmila Lapatsina; Raluca Fleischer; Ewan Smith; Valérie Bégay; Mirko Moroni; Luc Estebanez; Johannes Kühnemund; Jan Walcher; Edgar Specker; Martin Neuenschwander; Jens Peter von Kries; Volker Haucke; Rohini Kuner; James F A Poulet; Jan Schmoranzer; Kate Poole; Lewin GR

Nature Neuroscience 2017

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Pharmacological restoration and therapeutic targeting of the B-cell phenotype in classical Hodgkin lymphoma

  • Jing Du; Martin Neuenschwander; Yong Yu; J. Henry M. Däbritz; Nina-Rosa Neuendorff; Kolja Schleich; Aitomi Bittner; Maja Milanovic; Gregor Beuster; Silke Radetzki; Edgar Specker; Maurice Reimann; Frank Rosenbauer; Stephan Mathas; Philipp Lohneis; Michael Hummel; Bernd Dörken; Jens Peter von Kries; Soyoung Lee; Clemens A. Schmitt

Blood 2017

read online
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Kiwi store

  • fully automated storage of compounds at -20°C in low humidity < 30%
  • Total number of 220.000 compounds stored in 96-REMP tube racks
  • Storage of 200µl of 10mM DMSO solution in two copies.
  • Indentification: 1D-barcoded 96-racks with 2D-barcoded tubes at the bottom.
  • Individual sample access with tubepuncher module for hitpicking

Tecan evoware workstation

Freedom evo pipetting system

  • Hotel with thawing station
  • Gripper arm for transfer of plates and racks
  • Multi-channel-arm (MCA) with 96 tips and flexible LiHa Span 8 arm
  • Washing station for 96 MCA and 8 channel arm
  • REMP Capper/ Decapper
  • Ziath 1D- and 2D-barcode scanner

LC/MS TOF (Agilent)

  • Agilent 6200 Series TOF for high resolution mass spectrometry
  • Impurity testing, product degradation studies
  • Automated sample uptake and analysis system
  • measurement of 352 compounds on 384well MTP in a single run
  • Data for hit identity, integrity and purity for hitpicking plates
view into the Kiwi-store
view onto the worktable of the tecan evoware workstation
LC-tower with MS-TOF behind it

Kiwi store

  • fully automated storage of compounds at -20°C in low humidity < 30%
  • Total number of 220.000 compounds stored in 96-REMP tube racks
  • Storage of 200µl of 10mM DMSO solution in two copies.
  • Indentification: 1D-barcoded 96-racks with 2D-barcoded tubes at the bottom.
  • Individual sample access with tubepuncher module for hitpicking
view into the Kiwi-store

Tecan evoware workstation

Freedom evo pipetting system

  • Hotel with thawing station
  • Gripper arm for transfer of plates and racks
  • Multi-channel-arm (MCA) with 96 tips and flexible LiHa Span 8 arm
  • Washing station for 96 MCA and 8 channel arm
  • REMP Capper/ Decapper
  • Ziath 1D- and 2D-barcode scanner
view onto the worktable of the tecan evoware workstation

LC/MS TOF (Agilent)

  • Agilent 6200 Series TOF for high resolution mass spectrometry
  • Impurity testing, product degradation studies
  • Automated sample uptake and analysis system
  • measurement of 352 compounds on 384well MTP in a single run
  • Data for hit identity, integrity and purity for hitpicking plates
LC-tower with MS-TOF behind it

Alumni


Photos taken by Katy Franke