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In Vitro ADME


In Vitro ADME

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For early-stage compounds, we conduct a full panel of early ADME screening studies to investigate druggability. Despite our relatively short history, we have established a very successful track record in helping our clients with early stage programs by delivering 24 PCCs in combination with our pharmacology and medicinal chemistry units since 2008. To continue better serving our Western clientele, many of these services have now been extended to Plainsboro, NJ.

For later stage programs, definitive studies are conducted to profile which transporters and CYPs the drug interacts with as well as the resultant metabolic biotransformations. In all we have authored or contributed to 32 IND and 2 NDA programs since 2012. XBL has also established a strong track record with later stage development programs; more information can be found at http://www.xbl.com/.

Early ADME

  • Physicochemical properties: kinetic and thermodynamic solubility, logD, pKa
  • Permeability: PAMPA, Caco-2, MDR1-MDCK
  • Solution-phase stability
  • Metabolic stability: microsomes, hepatocytes, S9, recombinant CYPs, plasma from multiple species
  • CYP inhibition: 5-in-1 cocktail or discrete substrates, %inhibition or IC50 determinations
  • CYP induction: PXR-luciferase reporter gene assay for CYP3A
  • Protein binding: plasma, brain or tissue homogenate from multiple species
  • Blood-plasma partition: multiple species

Definitive ADME

  • CYP inhibition: 8 CYP isoforms, multiple substrates for CYP3A4, IC50, Ki, Kinact, reversible/irreversible inhibitor identification, time-dependent inhibition
  • CYP induction: human cryopreserved hepatocytes, enzyme activity and/or mRNA determinations
  • CYP phenotyping: multiple species
  • Aldehyde oxidase (AO): identification of AO involvement in drug metabolism
  • Protein binding: equilibrium dialysis, ultrafiltration, and ultracentrifugation
  • Transporters: MRP2, OATP1B1, OATP1B3, OAT1, OAT3, OCT1, OCT2 and BCRP (currently undergoing validation)

Met ID with Species Comparison in Human, Cyno Monkey, Dog, Rat and Mouse Liver Microsomes (LMs)

DMPK 1