Science Pool

Pneumonia induced by multidrug resistant (MDR) Acinetobacter baumannii strains is among the most common and deadly forms of healthcare acquired infections. Animal models play a critical role during the preclinical assessment of novel therapeutic approaches, however, only a self-limiting pneumonia with no or limited local bacterial replication is frequently obtained when MDR A. baumannii is the pathogen.

To strengthen and characterise a sustained lung infection model, in this publication, we focus on:

• the ability of intranasal inoculation, intratracheal instillation and oropharyngeal aspiration methods of administration of the bacterial challenge to induce a robust pneumonia in mice
• the characterisation of the infection model obtained after intratracheal instillation and oropharyngeal aspiration in terms of histopathological examination of pulmonary lesions, biomarkers of inflammation and leukocytes cells infiltration after treatment with either vehicle or with the antibiotic tigecycline efficacious into reducing lung bacterial load.

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Learn more about Evotec's regulated LC/MS bioanalysis capabilities and expertise including:

• High quality service across all phases of pre-clinical and clinical drug development in compliance with GLP and GCP regulations
• More than 25 years of experience to perform LC/MS activities in a regulated environment
• Extensive bioanalytical method development expertise to meet the most demanding and challenging client needs
• Multidisciplinary collaboration enabling integrated solutions to accelerate the drug development process

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This article published in Nature describes a first-in-class METTL3 inhibitor for the treatment of acute Myeloid Leukaemia.

The publication covers:

• Development of STM2457 following high-throughput screen
• Selectivity screening across the panel of 45 human methyltransferases
• Crystal structure of METTL3-14 complex with STM2457, part of structure-based drug design strategy for this target
• Compound validation in cellular assays and in vivo efficacy

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Learn more about Evotec’s polymerase chain reaction (PCR) services including:

• Therapeutic modalities
• Sample management capabilities
• PCR applications 
• Quantitative real time PCR (qPCR) and reverse transcription qPCR (RT-qPCR) applications, including copy number estimation assays, gene expression profiling and genotyping assaysRegulated PCR services

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Learn more about our ligand binding assays and how they can support biological drug testing in a regulated environment, including:

• Regulated bioanalysis
• Immunogenicity
• Immunotoxicity
• Biomarkers (safety and efficacy)
• Clinical Pathology
• Sample Management
• Additional activities

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Stable expression of recombinant protein therapeutics in CHO cells often relies on random or semi-random genomic integration events which results in a widely heterogenous cell population. This leads to significant effort in clone screening during cell line development in order to identify clones with high expression, growth and product quality. 

In this publication, we focus on:

• the development of two targeted integration systems that express high levels of recombinant protein in CHO cells by: 
  • the installation of rationally designed piggyBac-based chromosomal landing pads
  • the use of site specific recombinases including PhiC31 and CRE 
• demonstration of the functional integration of several donor vectors encoding various therapeutic proteins including two monoclonal antibodies and one Fc-fusion molecule

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Chikungunya virus, which is transmitted by mosquitoes, can cause disabling chronic arthritis. There are currently no medicines for prophylaxis of Chikungunya, or other viruses transmitted by Aedes mosquitoes, such as Dengue and Zika. Potential therapeutics have been identified, but to perform a successful chemoprophylaxis trial during a short Chikungunya outbreak requires an identified at-risk population. We examined the potential for application of a household transmission model, as used in testing prophylactic drugs against respiratory viruses, included influenza and COVID-19.

In this poster we:

• Set out the evidence for multiple Chikungunya infections occurring per household
• Describe how we are validating the secondary household infection rate
• Show how this could be used in future clinical trials to demonstrate prophylactic efficacy against chikungunya virus infection and other Aedes-mosquito-borne viruses

Read our poster to learn more about our research!

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In this article, we discuss the role of structure-based virtual screening in drug discovery. 

The publication covers:

• an overview of structural-based virtual screening and the importance of selecting the most appropriate protocol for affinity estimation calculations
• the development of an automated calibration process implemented in a Knime workflow consisting of 4 steps:
  • preparation of a protein test set with structures and models of the target
  • preparation of a compound test set with target-related ligands and decoys
  • automatic test of 24 scoring/rescoring protocols for each target structure and model
  • graphical display of the results
•  demonstration of the application of this tool in setting up an optimal protocol for structure-based virtual screening against Retinoid X Receptor alpha

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This article forms a book chapter in Quantum Mechanics In Drug Discovery which is part of the Methods in Molecular Biology book series.

In this article, we discuss the use of quantum mechanics in understanding receptor-ligand interactions and chemical reactions.

The chapter includes:

• an overview of the use of quantum mechanics methods in drug design and drug discovery
• presentation of the most popular quantum mechanics methods and software packages
• discussion of recent representative applications in drug design and drug discovery

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This article forms a book chapter in Artificial Intelligence in Drug Design.

In this review article, we discuss the use of machine learning approaches in large omics studies

The chapter includes:

• an overview of the typical analysis of an omics dataset using machine learning
• demonstration of how to build a model predicting drug-induced liver injury (DILI) using transcriptomics data
• best practices and pitfalls to consider during initial data exploration and model training through to validation and analysis of the final model

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