Research and discovery
Physicochemical analysis methods and expertise to aid selection of drug candidates based upon predefined Target Product Profiles
Drug discovery?and lead optimization are?the first?steps?needed?to enable?a successful drug product?to get to?market.?The key here is to identify compounds?that bind to the identified target protein with?the?desired?characteristics,?and to assess?the likelihood for?manufacturing?success?-?being?able to?process and formulate?the candidate molecule?into a drug product in an efficient manner.??
Due to the complex nature of molecule discovery,?there is a high risk of?failure, when compounds do not behave as expected, do not have the required activity,?or?show issues?during?development.??
Malvern Panalytical’s?toolset of physicochemical analysis solutions?aids?researchers to?make informed decisions about how the?characteristics of the?molecules and materials they are working?with?impact on?their behavior.?Our technologies and?expertise?help ensure?decisions are based on?the?best possible data:?they help?monitor and?optimize?sample?and assay?conditions,?and?validate?hits from high throughput assays?or fragment-based screening. This assists in?building?a more informed picture of the?interaction between?lead molecules?and?target?protein in terms of structure activity relationship?(SAR)?and underlying interactions.?Malvern Panalytical?solutions?can also?elucidate?the crystalline structure of?the API to enable patenting and future optimization of the new chemical entity?(NCE).
Quality control for assay development
To be confident in your results you need?robust and repeatable?data. This is where Malvern Panalytical can help you in a number of ways,?starting with understanding the quality and stability of?assay components such as?reagents, proteins?or compounds. Reagent control is?the basis for good assay development, and?reagent?stability, purity and functionality?must?be considered to achieve a robust assay.?
Watch the short videos, in the related content below, to see how our solutions can help with the following:
Make?sure your target protein is in good condition?
When screening many compounds; for example,?in a biosensor assay, it is critically?important?that the target protein?is active?and stable?under assay conditions.??An unstable or inactive target protein?could?compromise the assay, resulting in?costly?screening?iterations and potentially?even?false negative results.?
Address solubility issues with low molecular weight ligands
Solubility issues for low molecular weight (LMW) ligands?can also create?quality issues?in screening activities.?Problems?with?solubility can affect binding data and make?your ligand-ranking less reliable.? ?
Ensure all batches of target proteins are the same
Find out how?Isothermic Titration Calorimetry?is?used?in?quality control of different target protein batches.? ?
Assay development - related content
Case study 1 – sample quality control
Target protein quality causing problems in biosensor screening assay sharing, and how DLS and ITC can help. Watch the video
Case Study 2 - Protein batch to batch consistency
See how ITC is used in quality control of different target protein batches. Watch the video
Case study 3 – LMW ligands solubility issues
Problems with solubility can affect binding data and make ligand-ranking less reliable, see how DLS and DLS can help. Watch the video
Enzymes play a special role by catalyzing chemical reactions in the human body through binding to molecular substrates and modifying them in specific ways. Enzymes are important in drug discovery and development, as approximately half of current drug targets are enzymes. A lot of effort is put into discovery and characterization of enzymatic pathways and enzyme activity as well as developing drugs that interact with enzymes?
Enzymatic assays are among the most frequently performed activities in biochemistry and typically require use of labeled substrates and coupled reactions with spectrophotometric or chemical readout.? Isothermal titration calorimetry (ITC) offers a direct and generic way of following the rate of enzymatic catalysis through the heat rate associated with enzymatic reactions. Enzymatic assays in ITC can be run with opaque solutions at enzyme concentrations comparable to that used in biochemical assays and can yield a complete set of kinetic parameters in a single experiment.
Enzymatic Assays - Featured Content
Studying enzyme kinetics through Isothermal Titration Calorimetry
The use of ITC for obtaining enzyme kinetic constants
Use of isothermal titration calorimetry to investigate and identify novel peptide substrates for prolyl carboxypeptidase: a technology comparison
Focus on Pharma - Characterizing Enzyme Inhibition and Activation by ITC
Validation of hits from primary screens
?The hits?generated by?the high-?and medium-throughput screening assays?used in the early?stages of drug discovery?need validation?to?ensure they aren’t false positives; for example, if?they interact with a biochemical assay instead of?the target protein.?Isothermal Titration Calorimetry?(ITC)?can be used to confirm and quantify binding and?to?establish?binding?stoichiometries, so that false positives?and non-stoichiometric binders can be?discounted?and not?waste resource as the project progresses.??
Hear from one of our experts about how ITC can help:Watch the video
Mechanism of action analysis
Learn more about how it can be applied in this short video:Watch the video
Listen to this example of optimization of diaminopyrimidine renin inhibitors:Watch the video
Unterstützung der Arzneimittelforschung durch das Malvern MicroCal ITC mit Anwendungen von der Assay-Entwicklung bis zur Leitsubstanzoptimierung
Mehrfache Anwendungen für das Malvern MicroCal Auto-iTC200 in einem fragmentbasierten Wirkstoffforschungsprogramm
Addressing the needs of drug discovery with the MicroCal PEAQ-ITC instruments
Targeting protein/protein interactions in drug design
Quickly monitor the size and aggregation state of compounds and target proteins
Characterize your compound and control changes during early development. Provide the analytical information to support patents of new chemical entities
Validate high throughput binding assay results , and add thermodynamic information about the binding to your set of data.