The success of a
drug in the clinic is dependent on more than just activity against a specified
biological target. The integrated approach to drug discovery and development
taken by researchers at deCODE chemistry & biostructures allows our clients
to evaluate leads based on a range of pharmaceutical properties. Our Drug Safety
and Metabolism group uses a combination of in vitro and in vivo studies to
select and prioritize candidates to take forward into clinical evelopment. Early
identification of potential liabilities within a compound series using a variety
of in vitro predictive assays enables our clients to focus their resources on
the analogues that hold the most promise. As client programs transition from
lead optimization to candidate selection, our team evaluates the factors that
differentiate a drug from an interesting compound, including: determination of
approximate lethal dose, in vivo safety pharmacology, pharmacokinetics to match
an intended dosing regimen, and development of an appropriate formulation.
In Vitro ADME and Toxicology Absorption, distribution, metabolism, and excretion (ADME) are important
selection tools in deciding which drug candidates should be pursued for further
development. During the lead optimization phase of medicinal chemistry, our
chemists address multiple factors when selecting which series and, ultimately,
which molecules to advance into pre-clinical development. The scientists in our
Metabolism group work together with our chemists from an early stage to define
and refine the properties of the molecules using a range of tests. These include
metabolic stability (profiling against liver microsomes from multiple species),
cytochrome P450 inhibition, plasma protein binding, mutagenicity, cytotoxicity
and solubility. Our Bioanalytical group utilizes state-of-the-art
instrumentation to identify and quantitate metabolites generated both in vitro
and in vivo. We provide pharmacokinetic profiling including: study design and
protocol development, management of in-life dosing, bioanalytical method
development, sample analysis, and data analysis. The goal of these studies is to
identify compounds for our clients that have desirable pharmaceutical properties
and pharmacokinetic profiles. Compounds that meet these goals are most likely to
be successful in supporting the intended indication, and such data assist with
predicting the clinical and pre-clinical dosing regimen. At the conclusion of
these studies, deCODE chemistry provides a comprehensive report that is suitable
for use in support of your drug development regulatory requirements.
Safety and Toxicology Studies Our Drug Safety
and Metabolism group assists clients with the design and execution of studies
beginning as early as lead optimization and continuing through to IND-directed
safety pharmacology and toxicology studies. We provide services such as ADME
profiling and bioanalytical method development, data which are integrated into
the design and implementation of toxicology and safety pharmacology studies.
These data can help with the choice of appropriate species for use in safety
testing. We perform acute and non-GLP range-finding toxicity studies to not only
define the dosages for definitive GLP studies, but also determine the amount of
active pharmaceutical ingredient (API) that will be required. By calling upon
our capabilities in API synthesis, we can arrange for appropriate amounts of
material to be produced to ensure successful completion of studies leading to an
IND. Definitive toxicology studies, safety pharmacology studies, and
mutagenicity studies are all carried out under the supervision of our toxicology
staff. Clients utilize our Drug Safety and Metabolism expertise to assist in
developing a data package that includes appropriate reports, IND summaries, and
overview as well as appropriate information for your Investigator's Brochure.
deCODE chemistry can assist you from candidate selection to IND, quickly,
safely, and cost-effectively.
