Developing a drug is an extremely long and regulated process. It globally includes a drug discovery phase, during which drug candidates are identified, and a preclinical phase where drug candidates have to demonstrate their proof-of-concept.
The drug discovery phase will include a step of understanding the mechanism of action on a molecular level. When a target is identified, screening compounds using a simplified model in vitro, in silico, or molecular. And once a lead is identified, it will be chemically modified to enhance its properties, such as its specificity, efficacy, or stability. Information collected during the screenings or the usage of a model will be used to benchmark the new leads and thus can be critical for the development of a new drug.
However, the testing strategies, and finding associated models, can be confusing, as the many options of screenings and models, and the requirements to put the testing in place are high, whether in equipment or in expertise.
This is why Labtoo developed a tailor-made service to support Labs, Biotechs, Medtech, and Pharma companies in their research program outsourcing.
Labtoo can be mandated in a fully customized mission to look for any type of testing models like HTS, HCS, and biochemical models. We work with academia and service labs to look for the best models and testing facilities according to specific needs.
High throughput screening (HTS) or high content screening (HCS) are techniques that aim at studying and identifying, within chemical and target libraries, molecules with novel and biologically active properties. Screening consists of using a large number of molecules in a biochemical or cellular test, which must be particularly robust, reproducible, and if possible inexpensive.
The biochemical model is used in the discovery of candidates. The advantage of this type of model is to limit the number of molecular actors and thus validate a target or mechanism of action. FRET and HTRF techniques applied to biochemical models are particularly effective in studying the phosphorylation and signaling pathways of molecules.
The formulation is a critical step in drug development and partly determines the success of a drug's market entry. The aim is to propose the solution best suited to the nature of the pharmaceutical ingredient candidates, their therapeutic target, and the route of administration envisaged.
The development of a "small molecule" drug candidate requires tools directly derived from chemistry. In this case, the de novo synthesis of the molecule, the search for candidates in chemical libraries, and the possibility of modifying these molecules by labeling techniques.
Perform a feasibility study by looking for existing expertise available within the network of partners
Set up a study protocol, financial quotation and preparing contracts with lab partners
Implement the study plan into a schedule, collect all needed materials and reagents and execute the service
The different drug development phases involve a large number of actors with different capacities.
Academic structures are involved in the development of drugs, particularly at the level of the in vitro and in vivo studies they can propose.
Some very expensive equipment may also be required (e.g. for mass spectrometry or robots for HTS screening) - in this case, academic platforms may be asked by private companies to support them.
Service companies for experimentation
Many service companies produce tools in drug discovery or development. This concerns in vitro tests for example, or formulation optimization. Other companies are specialized in regulatory testing, such as PK/PD and toxicity experiments.
These companies are often required to work under Good Laboratory Practice (GLP) conditions.
Service companies for production
Anticipating the drug production during its development is an early process: a marketed molecule has to be manufactured in very particular conditions (good manufacturing practice, GMP). The GPM production is not necessary for research use and preclinical studies, but commercial and clinical batches have to meet the GMP conditions.
Cell models, if appropriately designed, can be used to rapidly identify the molecular mechanisms of human diseases and develop new therapies.
The design of a robust, reproducible, relatively easy-to-read test (it should use quantifiable molecular markers) is particularly appropriate when using a molecule library for high-throughput screening.
As soon as the model is designed, the experimenter raises the question of how to quantify the expected effect: either by molecular markers or by phenotypic observation.
A molecular marker that is well identified and characterized in a pathology or cellular process has the great advantage of limiting observations linked to an indirect effect.
The FRET technique typically proves to be relevant when studying conformational changes (e.g. intracellular nuclear receptors), aggregation (especially in neurodegeneration), or measurement of receptor-ligand interactions. FRET is based on the transfer of energy between two fluorophores, possible when the two molecules are physically close. Other methods for measuring molecular markers, such as qPCR or dPCR for modulation of gene expression, ELISA or Western Blot for protein quantification, etc., are also available.
Microscopy and imaging in general are useful in phenotypic studies.