Source Name: 2020_Le Roux

Literature Information

  Peptides List

  Statistics

Literature Title Structure-Permeability Relationship of Semipeptidic Macrocycles-Understanding and Optimizing Passive Permeability and Efflux Ratio
Doi 10.1021/acs.jmedchem.0c00013
Research Group
  1. Département de Pharmacologie-Physiologie, Institut de Pharmacologie de Sherbrooke
  2. Drug Discovery, Pharmaceuticals, Bayer AG
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Data Number 47
Minimum Molecular Weight 342.4
Maximum Molecular Weight 486.7


Assay Information 1

Assay Type PAMPA
Permeability Type logPe
Membrane Measurement Direction (Exclude PAMPA) -
Assay Detail Permeability was assessed using Millipore 96-well multiscreen filter plates with polyvinylidine fluoride membranes and transport receiver plates (Millipore). The artificial membrane was prepared by adding 5 μL of 1.8% lecithin in dodecane to the acceptor well and overlayed with 300 µL of PBS. After addition of 300 µL test compounds at 10 µM to the donor plate, it was placed in the acceptor plate and incubated for 16 hours at 25°C. Compound concentrations were determined by LC-MS/MS and the effective permeability was calculated. The effective permeability (Pe), in units of centimeter per second, was calculated using the following equation: LogPe = Log{C*[-ln(1-([drug]acceptor/[drug]equilibrim))]}.
The compounds can be categorized into high and low permeability. Generally speaking, compounds which have a -Log Pe < 6 are classified as high permeable whereas compounds with a -Log Pe > 7 are classified as impermeable. Testosterone was used as positive control while Methotrexate was used as negative control. The PAMPA assay was performed at Pharmaron.


Assay Information 2

Assay Type Caco2
Permeability Type logPapp
Membrane Measurement Direction (Exclude PAMPA) Average of Apical to Basolateral (AB) and Basolateral to Apical (BA)
Assay Detail The Caco-2 assay was performed as described previously (Gnoth, M. J.; Sandmann, S.; Engel, K.; Radtke, M. In vitro and in vivo comparison of the subtrate characteristics of sorafenib tosylate toward P-glycoprotein; Drug metab. Disp. 2010, 38, 1341-1346). Caco-2 assay was performed at Pharmaron, using Sulfasalazin, Metoprolol and Cimetidine as control.