SERVICES
DMPK
Bridging the gap between in vitro and in vivo data sources, we continually provide critical insights that give candidate selection the Leading Edge™.
Reliability
Data you can trust
Reliable data is essential for decision-making, and the most important element you need for your program. Not all data is trustworthy. We have identified multiple flaws in more than 30% of the assays being run by other groups. With our team, you’ll have primary, on target in vitro screening data that you can trust. Partnering with NuChem gives you the skill and reliability needed for project success.
Adaptability
Cutting-edge services
Take your projects to the next level with our in vitro biology capabilities. The cutting-edge services you can access with our team include developing assays & biomarkers, screening, expert consulting, biochemical & cellular assays and ADME-PK. Our capabilities are constantly evolving, and provide flexibility for your specific needs.
Expertise
An unparalleled knowledge base
Accelerate small molecule programs with the comprehensive ADME studies we provide. Any in vitro ADME studies required for your compounds can benefit from our extensive experience with cell biology, enzymology, and bioanalysis. From discovery to pre-IND stages, our team has the expertise required. Access our experience with in vitro models using liver fractions or primary hepatocytes to investigate metabolic stability, clearance or the metabolite profile of drug candidates.
Collaboration
Data you can trust
Getting the maximum value out of collaborative work requires a certain mindset. With our team, you benefit from our ability to manage communication and logistics for project success. When working collaboratively, our team shares knowledge so our experience becomes your advantage.
Gain critical insights and reliable DMPK services with NuChem as your trusted partner.
Drug Discovery Screening for Lead Compound Selection
After target validation and hit identification, the chemical and enzymatic stability of new chemical entities should be performed to identify the most stable compounds during the intestinal transit and absorption while having minimal degradation by first-pass metabolism.
ADME screening services (full package or tailored studies) help you to select compounds with the best chance of giving an ideal pharmacokinetic profile.
Absorption
The PAMPA assay is rapid and produces data quickly for screening purposes.
The MDCK affords permeability data with a good correlation with the Caco-2 assay with a shorter culture time (5-day vs 21-day for the Caco-2).
The Caco-2 monolayer is the best in vitro model for the prediction of in vivo absorption and the most relevant in vitro model for the prediction of absorption and first-pass metabolism.
Chemical & Metabolic Stability
A good lead candidate is a compound with no undesirable functional group or no chemical reactivity. To screen out those structures, a compound is incubated:
– with GSH (chemical reactivity),
– with GSH and glutathione S-transferase (GST) to select the most stable compounds.
NuChem scientists can determine the metabolic clearance, biotransformation, and elimination pathways in vitro of your lead candidates to ensure that a good exposure (AUC) is achievable in vivo.
Ideal Candidates with Drug-Like Properties
- Comply with Lipinsky’s rule of 5
- Permeability > 3X10-6 cm/sec
- in vitro microsomal stability T1/2 > 45 min
- in vivo bioavailability > 35%, and half-life > 2 h
DMPK Services
Pharmacokinetic (PK) Studies
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LC-MS/MS method development
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Plasma or whole blood
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CSF or tissue homogenates
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Different administration routes (IP, PO, etc.)
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Phoenix WinNonlin software
Chemical Stability & Solubility
- SGF/SIF & plasma stability
Absorption/Permeability
- Pampa
- MDCK (transcellular absorption)
- Caco-2 (Bi-direction & efflux transporters)
Protein Binding
- Albumin, plasma, brain tissue, whole blood
- Blood to plasma ratio
Metabolism
- Metabolic stability, hepatic intrinsic clearance
- Oxidation and conjugation pathways
Elimination
- Excreta analysis of metabolites and parent compound
Data Analysis and Report Production
- Summary report for discovery lead selection
- Detailed report for IND filing