Source Name: 2015_Lewis

Literature Information

  Peptides List

  Statistics

Literature Title A Detailed Investigation on Conformation, Permeability and PK Properties of Two Related Cyclohexapeptides
Doi 10.1007/s10989-014-9447-3
Research Group
  1. Novartis Institutes for BioMedical Research, Novartis Pharma AG
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Data Number 2
Minimum Molecular Weight 712.9
Maximum Molecular Weight 755.0


Assay Information 1

Assay Type PAMPA
Permeability Type logPe
Membrane Measurement Direction (Exclude PAMPA) -
Assay Detail Parallel artificial membrane permeability assay is a primary screen surrogate for gastro-intestinal permeability (passive diffusion). PAMPA assay uses a thin hexadecane layer as a model membrane. The assay is carried out in 96-well plates where the ability of the compound to diffuse from a donor to an acceptor compartment separated by a hexadecane layer coated on a polycarbonate filter plate is measured. To minimize solubility issues compounds are loaded at 5 lM in the donor compartment and the assay buffer contains 5 % DMSO. The permeability is derived from the compound concentration (measured by LC–MS/MS) in the acceptor compartment after a 4-h incubation time.


Assay Information 2

Assay Type MDCK
Permeability Type logPapp
Membrane Measurement Direction (Exclude PAMPA) Apical to Basolateral (AB)
Assay Detail Madin Darby canine kidney (MDCK) cells are an epithelial cell line of canine kidney origin. MDCK cells have low expression of transporter proteins and low metabolic activity. MDCK cells are used as a cellular barrier model to assay polarized transport of compounds of interest through the epithelia. Under standard cell culture conditions, MDCK cells develop tight junctions and form monolayers of polarized cells. The cells are seeded on a 24 well plate (BD Falcon) and form a confluent monolayer within 4 days prior to the experiment. On day 4, the test compound is added to the apical side of the membrane and the transport of the compound across the monolayer is monitored after a 2 h incubation period.
For studies related to drug efflux, it is also necessary to examine the transport of the compound from the basolateral compartment to the apical compartment declared as efflux ratio. The permeability in both directions A to B and B to A are derived from the compound concentration (measured by LC–MS/MS) in apical and basal compartments after a 2-h incubation time.