© Fraunhofer ITMP | Bernd Müller

Drug Screening & Compound Repurposing

For Drug Screening & Compound Repurposing, we offer a comprehensive High-Throughput Screening, Hit validation and profiling capability, supported by a bioinformatics and IT infrastructure to aid rapid data processing and decision making. The primary focus of our work is the development of biologically relevant and screening compatible assays in the most common microtiter plate formats for use in biomedical research, chemical biology and drug discovery. These assays encompass the major protein target classes with readouts in all optical, label-free and High Content imaging technologies and can be operated making use of our fully integrated robotic screening platform. There are several small molecule screening libraries available, which include collections of up to 200,000 diverse compounds as well as target class focused, natural product and drug repurposing sets including approved drugs that have reached clinical use across 600 indications and pre-clinical compounds of varying degrees of validation, supported by a curated database. The selection of compounds for Hit to Lead progression takes place following mechanism-of-action, selectivity and ADMET studies aided by bioinformatics support.

 

Core competencies:

  • State of the art tools and technologies for developing innovative assays
  • Assay readout technologies include optical, label-free and high content imaging
  • Access to a variety of small molecule compound libraries
  • Triaging of compounds using mechanism-of-action, selectivity and ADMET profiling
  • Delivery of high quality compounds as starting points for drug discovery
  • Expertise in progressing compounds to industry standard Lead and Candidate milestones

Best practice in in assay development and screening

Expertise in developing of a broad range of assays, from biochemical assays to phenotypic or highly complex cell-based assays that make use of primary cells and induced pluripotent stem cells.

Access to compound libraries

Availability of compound libraries to address all chemical biology, drug discovery and drug repurposing projects. Information relating to the compounds can be shared with partners in order to allow selection of customized sets of compounds.

Provision of automated screening infrastructure

Most assays are developed in microtiter plate formats so they can be rapidly screened against our compound libraries. The screening activities take place using a state-of-the-art automated screening system with integrated liquid handling and reader devices. All raw data is accessed remotely and processed rapidly to identify active compounds for progression in the respective project value chain.

Development of critical paths for chemical biology and drug discovery projects

Our personnel have diverse backgrounds having been employed in academia, biotech and the pharmaceutical industry. They have the experience and track-record of developing critical paths that enable project progression to industry standards. A major focus is ensuring projects assets can be packaged for further progression.

Coronavirus research

A number of projects aiming to identify drugs against coronavirus are ongoing and yielding exciting results. These include:

The Fraunhofer ITMP screened a drug repurposing library to identify compounds that inhibited viral induced cytotoxicity of human epithelial cell-line. A number of previously unreported active compounds were identified and are now entering projects for their further development.

 

DRECOR (Development of new inhalation therapies by drug repurposing)

Identifying high quality molecules from drug repurposing screens to target the lungs and airways following their formulation for inhaled or systemic administration. Tissue- and cell type‑specific nanoparticular drug delivery systems and a prototype of a smart medical device for inhaled administration for use in clinical trials will be created.

Partners: 6 Fraunhofer institutes (IME, IGB, ISC, IBMT, IAP, IZI) and Fraunhofer Project Center for Drug Discovery and Delivery at Hebrew University of Jerusalem (Israel).

Additional Information

 

 

Exscalate4Cov

Using a combination of high performance computing power and AI with biological processing, the Exscalate4Cov consortium has successfully identified a potential treatment against coronavirus. Raloxifene has emerged as a promising molecule that could be effective in blocking the replication of the virus in cells, and could thus halt progression of the disease. In October 2020, the Italian Medicines Agency (AIFA) authorized the clinical study of this compound as a potential treatment for covid paucisymptomatic patients who are in hospital or at home.

Partners: 18 member institutions from seven European countries.

Additional Information

 

C-CNS

This project promotes scientific and technological exchange between Germany and Japan in order to address medical and socio-economic challenges of both countries. The Japanese partner is the Institute of Biomedical Research and Innovation based in Kobe. The disease focus is stroke and other neurodegenerative diseases that are prevalent in the elderly of both partner countries and a significant burden on society. The partners have worked closely in developing assays that are releavant to stroke and are currently identifying compounds as potential stroke therapies to treat this life threatening event. In addition to this, scientific exchange visits have taken place to provide training in assay development and screening.

Partners: Fraunhofer EMB, Prof. Dr. Johannes Boltze; Institute of Biomedical Research and Innovation, Kobe, Japan, Prof. Dr. Akihiko Taguchi.

Additional Information

Neglected tropical diseases

Research teams from Europe, Africa and South America undertook drug development for neglected infectious diseases including leishmaniasis, Chagas disease, sleeping sickness, schistosomiasis and malaria. Together, these diseases affect more than a billion people worldwide. The research teams successfully established a common high capacity drug discovery platform, where the Fraunhofer ITMP developed a number of assays, performed screening campaigns and ADMET studies that resulted in multiple Hit and Lead series and one Candidate molecule.

Partners: 20 member institutions from Europe, Africa and South America.

Additional Information:

New Medicines for Trypanosomatidic Infections

Parasite-specific cyclic nucleotide phosphodiesterase inhibitors to target Neglected Parasitic Diseases

Ellinger B, Bojkova D, Zaliani A, Cinatl J, Claussen C, Westhaus S, Reinshagen J, Kuzikov M, Wolf M, Geisslinger G, Gribbon P, Ciesek S.
Identification of inhibitors of SARS-CoV-2 in-vitro cellular toxicity in human (Caco-2) cells using a large scale drug repurposing collection. 
doi: 10.21203/rs.3.rs-23951/v1

 

Kikuchi-Taura A, Okinaka Y, Takeuchi Y, Ogawa Y, Maeda M, Kataoka Y, Yasui T, Kimura T, Gul S, Claussen C, Boltze J, Taguchi A.
Bone Marrow Mononuclear Cells Activate Angiogenesis via Gap Junction-Mediated Cell-Cell Interaction. 
Stroke. 2020 Apr;51(4):1279-1289
doi: 10.1161/STROKEAHA.119.028072

 

Takeuchi Y, Okinaka Y, Ogawa Y, Kikuchi-Taura A, Kataoka Y, Gul S, Claussen C, Boltze J, Taguchi A.
Intravenous Bone Marrow Mononuclear Cells Transplantation in Aged Mice Increases Transcription of Glucose Transporter 1 and Na+/K+-ATPase at Hippocampus Followed by Restored Neurological Functions. 
Front Aging Neurosci. 2020 Jun 11;12:170
doi: 10.3389/fnagi.2020.00170

 

Moraes CB, Witt G, Kuzikov M, Ellinger B, Calogeropoulou T, Prousis KC, Mangani S, Di Pisa F, Landi G, Iacono LD, Pozzi C, Freitas-Junior LH, Dos Santos Pascoalino B, Bertolacini CP, Behrens B, Keminer O, Leu J, Wolf M, Reinshagen J, Cordeiro-da-Silva A, Santarem N, Venturelli A, Wrigley S, Karunakaran D, Kebede B, Pöhner I, Müller W, Panecka-Hofman J, Wade RC, Fenske M, Clos J, Alunda JM, Corral MJ, Uliassi E, Bolognesi ML, Linciano P, Quotadamo A, Ferrari S, Santucci M, Borsari C, Costi MP, Gul S.
Accelerating Drug Discovery Efforts for Trypanosomatidic Infections Using an Integrated Transnational Academic Drug Discovery Platform. 
SLAS Discov. 2019 Mar;24(3):346-361
doi: 10.1177/2472555218823171

 

Salado IG, Singh AK, Moreno-Cinos C, Sakaine G, Siderius M, Van der Veken P, Matheeussen A, van der Meer T, Sadek P, Gul S, Maes L, Sterk GJ, Leurs R, Brown D, Augustyns K.
Lead Optimization of Phthalazinone Phosphodiesterase Inhibitors as Novel Antitrypanosomal Compounds.  
J Med Chem. 2020 Apr 9;63(7):3485-3507
doi: 10.1021/acs.jmedchem.9b00985