VIDA

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Title of the project:

VIDA

Teasertext:
Bioinformatic, biophysical and cell biological methods to reduce attrition rates of clinical drug candidates
Project name:
VIDA
Start:
01.09.2020
End:
31.08.2022
Project leader:
Dr. Martin Kriebel
Project funding:
  • BMWi
Project management:
  • VDI/VDE Innovation + Technik GmbH
Funding reference number:
16KN073202
Text:

The clinical phases of drug development are characterized by high attrition rates of newly developed substances and associated high costs. This can be remedied by new methods for the design of new active compounds and improved drug analysis, which lead into translational, functional preclinical tests.

Using the example of the development of new drugs for the treatment of anxiety disorders, the VIDA consortium is developing: 1) in silico methods for modeling and predicting on-target and off-target binding, 2) biophysical analysis methods for characterizing on-target binding of potential drug candidates in physiological environments, 3) robust, phenotypic test systems as an indispensable preliminary stage of successful clinical trials.

Description:

In the course of drug development, about two thirds of all synthetic drug candidates fail in early development phases. The reasons are mainly insufficient selectivity towards the actual target structure (off-target effects), resulting side effects and, as a consequence, missing or not clearly assignable treatment effects.

In order to increase the productivity of preclinical development phases, the project partners 2bind GmbH, NMI and PharmAI GmbH are developing innovative preclinical procedures and tests using the example of new active compounds for the treatment of anxiety disorders. As a scientific basis, the consortium uses research results from the NMI that indicate a disrupted inhibition of neurons of the central nervous system (CNS) as a cause of anxiety disorders. First results show that so-called mimetic peptides can be used to address cellular mechanisms that contribute essentially to the stabilization of necessary inhibitory circuits in the CNS. Due to their structure and binding properties, the latter peptides serve as templates for the development and characterization of novel synthetic drug candidates with pharmacokinetic properties superior to peptide structures for the treatment of anxiety disorders.

As a partner from the field of bioinformatics, PharmAI GmbH is developing an innovative in silico method for the identification of new small molecule drug candidates, which considers both on and off target interactions. Based on the structure of selected mimetic peptides, this allows the identification of new drug candidates as well as already available and patentable substances (drug repositioning) with corresponding properties.

2bind GmbH contributes novel biophysical analysis methods based on MicroScale Thermophoresis (MST) and Biolayer Interferometry (BLI) to the project network. This enables the analysis of small molecule drug candidates with regard to on-target interactions in a near physiological environment (i.e. in the presence of off-targets).

The NMI provides robust and translational preclinical test systems based on relevant cell culture models. These multiparametric approaches will allow quantitative mode-of-action and phenotypic analyses of synaptic stability after the application of drug candidates to be tested.

After successful completion of the project, these novel and target-oriented methods will be available to pharmaceutical companies as a service and will accordingly expand the portfolios of 2bind GmbH, NMI and PharmAI GmbH.

Project partners:
  • 2bind GmbH
  • PharmAI GmbH
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