In Vitro ADME-Tox Profiling

It is estimated that about half of the drug candidates fail in clinical trials because of unacceptable efficacy (mainly attributed to poor bioavailability due to undesirable metabolic stability and ineffective intestinal absorption) and toxicity. Thus, the identification of the absorption, distribution, metabolism, excretion (ADME) and toxicological (Tox) properties of compounds at an early stage using appropriate assays would be expected to ensure that the most desirable compounds are tested in clinical trials. This "fail early and fail cheap" strategy is often exploited by the pharmaceutical industry as an effective way to reduce attrition in the drug discovery process. Creative Biostructure provides MagHelix™ in vitro ADME-Tox assays to assess the metabolism, bioavailability, pharmacology, and toxicology of compounds and help you make full use of all ADME-Tox profiling data to prioritize candidates.

An example of a compound merging attempt.

ADME-Tox assays in the early stage can be integrated with medicinal chemistry and structure optimization, assessing the following properties of a compound: aqueous solubility under physiological conditions, metabolic and chemical stability, membrane permeability, and inhibition of major metabolic enzymes (e.g., Cytochrome P-450). In addition, cytotoxicity, cardiotoxicity, metabolism, off-target liability, and other types of in vitro ADME-Tox assays should be implemented as early as possible in the drug discovery progress.

Our in vitro ADME-Tox profiling services include but are not limited to:

Physicochemical Profiling
  • Turbidimetric solubility
  • Thermodynamic solubility
  • Chemical stability
  • pKa
  • Lipophilicity (logP and logD) …
In Vitro ADME and PK
  • Metabolite profiling and identification
  • Microsomal binding and stability
  • S9 metabolic stability
  • Plasma protein binding and stability
  • Cytochrome P450 induction
  • Cytochrome P450 inhibition
  • PAMPA
  • Caco-2 permeability
  • MDCK-MDR1 permeability
  • Red blood cell partitioning
  • Evaluation of transporter interactions…
Toxicology
  • hERG safety
  • Functional mitochondrial toxicity assay
  • Drug-drug interactions
  • Ames tests for mutagenicity
  • Cytotoxicity assays against human cell lines…

Capabilities and advantages of our in vitro ADME-Tox profiling services:

  • Automated and high-throughput techniques and equipment are utilized to perform in vitro screening assays to ensure cost-effectiveness.
  • Innovative cell and tissue models such as 3D cells and organ-on-chip improve screening results.
  • Experienced scientists propose appropriate experimental strategies according to specific project requirements and assist in data analysis.
  • Our in vitro ADME-Tox profiling services follow regulatory guidelines and we have confidence in the quality of the data.
  • We also support in silico predictions of pharmacokinetic and toxicological properties.

Creative Biostructure provides sophisticated and strategic customized MagHelix™ in vitro ADME-Tox profiling for drug discovery in a cost-effective and time-saving way. Our in vitro assays can significantly save much of your precious time and quickly screen out several effective drug candidates. Our experienced team of scientists has actively cooperated with leaders of chemistry, biotechnology, and pharmaceutical industries, involving in high-throughput drug screening, hit identification and validation, hit to lead process, lead optimization, and preclinical assays.

Reference

  1. Chung T D Y.; et al. In vitro and in vivo assessment of ADME and PK properties during lead selection and lead optimization–guidelines, benchmarks and rules of thumb. Assay Guidance Manual. Eli Lilly & Company and the National Center for Advancing Translational Sciences, 2015.
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