Our areas of ADME/DMPK expertise
| Plasma and tissue protein binding |
| Plasma and tissue protein binding affect the availability and pharmacokinetic properties of the drug compound. In plasma, the bind compounds typically bind in various amounts to the abundant proteins – albumin, globulins and alpha-1-acid glycoprotein. We provide various accurate ways to assess compounds’ PPB capability. |
 Find out more on our plasma and tissue protein binding and stability services
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| PAMPA, Caco-2, MDCK and skin permeability |
| Drug molecules typically need to traverse through various biological membranes in order to reach their target molecules. Permeation ability is thus a key property for good bioavailabilty. We provide expertise in synthetic and cell based in vitro and ex vivo permeation models. |
Find out more on our permeation models
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| Metabolite identification and stability |
| Identification of the metabolites, the involved metabolism enzymes and stabilities of the metabolites is a key area in ADME studies. We provide excellence in metabolism studies as well as instrumentation needed for the detection of the small amounts of metabolites. Our metabolism studies include both in vitro and in vivo models. |
Find out more on our metabolism expertise
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| Reactive metabolite characterisation |
| Reactive metabolites are metabolites able to form covalent adducts with cells nucleic acids and proteins. Reactive metabolites are thought to be one major concern in idiosyncratic toxicity, typically manifesting as drug induced liver toxicity (DILI), skin and hematopoietic reactions. In addition to typical triple quadrupole LC-MS/MS analysis, we provide more sensitive acurate mass analytical methods for detection of reactive metabolites. |
Find out more on our unique expertise in reactive metabolites characterisation
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| Metabolites in safety testing (MIST) |
| Metabolites can cause a safety concern, which not be captured by the classical preclinical in vivo toxicity testing. This is mainly due to the differences in metabolism in different human and difference preclinical species. MIST concept is promoted by regulatory authorities to assess these safety concerns early during drug discovery and involves identifying the metabolites and their stability/abundance in various preclinical species in addition to human. |
Find out more on our MIST expertise and studies
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| CYP P450 identification, inhibition and induction |
| Identification of the metabolising CYP enzyme(s) is needed to understand the biotransformation profile of the compound and also possible population level differences in metabolism due to polymorphisms in CYP genes. In addition, the compounds ability to inhibit or induce CYP enzymes can lead to concerns in drug interaction or altered metabolism of the endogenous molecules. |
Find out more on comprehensive CYP expertise
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| Pharmacokinetics and bioanalytics |
| Pharmacokinetics is a key aspect in lead optimization, where the compounds stability, bioavailability and tissue distribution is studied. We can provide fast an end-to-end PK solutions, from in life part with various dosing routes, rodent and non-rodent models to bioanalytics and PK calculations. Our bioanalytics can measure both the parent and identified metabolites from the samples. |
Find out more on our total fast pharmacokinetics solutions
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| In vivo disease models are the key step to develop the compounds efficacy fomr the typical in vitro assays to real in vivo models. We provide in vivo models in the areas of type I and II diabetes, cardiovascular, hypertension and stroke, oncology and gastro-intestinal areas with full analytics options. We tailor the efficacy model studies and analytics for each customer and project. |
Find out more on our disease models
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| Assessing compounds toxicity dring the lead optimization is a very important aspect and should be in conjunction with the pharmacokinetics studies and planning the in vivo efficacy models. We provide both early non-GLP and regulatory preclinical GLP toxicology studies. Our uniqueness comes from our 360-degree toxicology platform – combining in silico, in vitro and in vivo toxicology expertise |
Find out more on our in silico, in vitro and in vivo toxcilogy expertise
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| In silico ADME property prediction |
| Our proprietary QSAR models of the physicochemical properties are based on experimentally measured values of a large collection of small molecules, followed by statistical data mining algorithms. This enables prediction of physicochemical properties for novel compounds. |
Find out more on our in silico ADME property prediction
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| In silico bioactivity and toxicity prediction |
| Our proprietary Ontomine in silico platform is an expert system, trained by data form over 100.000 real compounds experimentally measured target binding, toxicity and adverse effects. This knowledgebase and data analysis algorithms enable predictions for novel compounds. |
Find out more on our Ontomine in silico platform
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| Experimental logP, logD, logS, pKa analysis |
| We perform weekly various physcicocemical property measurements in our laboratories. These measurements are typically done for compounds in early stages of drug discovery in a process to leading to gain the drug like properties. |
Find out more on experimental logP, logD, logS and pKa analysis
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Follow this link to get a list of our available ADME studies
Request a quote for ADME/DMPK study
All our studies can also be tailored on customer’s request.
Contact us from this link.
Background
The lead optimization process aims to improving the hit/lead molecules properties for ADME profile, reduction of off-target effects and improved efficacy. Series of compounds with altered properties are assayed and their drug like properties are optimized.
Lead optimization process is balancing between multiple properties, including efficacy, safety and toxicity, chemical stability, metabolite formation, routes and stability, solubility and absorption. Ability to handle this process requires expertise and technologies from multiple disciplines.
A key aspect in ADME/DMPK lead optimization studies is to have a deep understanding on the various methods and study types, the aims of the discovery project and the characteristics of the molecule(s). The different ADME studies, including in silico, in vitro and in vivo, should not be seen as independent experiments, but as part of the whole process to rank compounds and optimize their properties, to be developed from the typical efficacious hits to drug like candidates.
Going with a service provider that only has the deep expertise in some of these areas (in silico, in vitro and in vivo) easily gets lost into expanding in studies in the particular expertise area, instead of understanding the whole approach of the lead-optimization project.
SBW Lead optimization platform
Our uniqueness comes from our ability to provide our customers with comprehensive expertise and technologies for the lead optimization process. This includes in silico, in vitro and in vivo technologies. We help our customers in all stages of the lead optimization process – planning the projects and individual studies – executing the in silico, in vitro and in vivo studies – interpreting the results and suggesting the followup actions. This is part of our Scientific Account Management strategy, where the studies are tailored for each account, project and molecule.
However, not just providing the highest expertise in these areas, our aim is to help our customers to understand the whole lead optimization process and plan each project with the right sequence of the various in silico, in vitro and in vivo studies, including the physicochemical studies, metabolism and drug interaction studies, permeation studies, pharmacokinetics studies, toxicology and safety studies as well as the in vivo efficacy studies. This also includes the scientific judgment of selecting the correct preclinical in vivo species for the various studies.
Our expertise can help you also to understand the studies done previously in other laboratories and how the results should interpreted – what is behind the numbers of the done analytics and what should be the next steps forward. In addition, we help you to understand the results from different done studies to see the whole picture in depth and plan the next steps. As a point differentiating us from other CROs, is our broad in deep understanding and daily operations in the various in silico, in vitro and in vivo areas. We are able to provide all this cross-disciplinary expertise by our Scientific Account Management process, get you forward faster, doing the correct tests and avoiding possibly un-necessary studies.
