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Bernardon J.-M.; Nedoncelle, P. WO1999\/010308; 4 March, 1999; Biadatti, T.; Roye, O. WO2005\/056516; 23 June, 2005; Biadatti, T.; Dumais, L.; Soulet, C.; Talano, S.; Daver, S. WO2006\/066978; 29 June, 2006; Biadatti, T.; Thoreau, E. WO2007\/068580; 21 June, 2007; Biadatti, T.; Thoreau, E. WO2007\/068579; 21 June, 2007."},{"key":"10.1016\/j.bmcl.2018.04.036_b0055","unstructured":"Pharmacological assays performed were as follows: Reporter gene assays were developed from the HG5LN cell line, which is a HeLa-derived cell line containing a luciferase reporter gene driven by a pentamer of the yeast transactivator GAL4 recognition sequence in front of the \u03b2-globin promoter. These HG5LN cells were then stably transfected with the GAL4 DNA-binding domain (DBD) fused to the ligand-binding domain (LBD) of the RAR alpha, RAR beta and RAR gamma receptors. Upon binding of the evaluated compounds, the receptor activity will be modulated leading to a specific modulation of the luciferase expression monitored by the measurement of well luminescence. Cells were seeded in microplates (10 000 cells per well) in culture medium supplemented with 10% fetal bovine serum and incubated for 4 hours at 37\u00b0C, 5% CO2. Serially diluted compounds (10 000\u20130.5nM, 0.1% DMSO) were then added to each well and the plates were incubated for 18h at 37\u00b0C, 5% CO2. Luciferase substrate (Promega P\/N# E2980) was added to each well and the emitted luminescence read on a plate reader. Relative luminescence units (\u2018RLU\u2019) were normalized using the averaged positive controls (\u2018POS\u2019 containing a saturating concentration of the reference agonist, ie TTNPB) and negative controls (\u2018NEG\u2019 containing DMSO):% inhibition=((RLU-NEG)\u2217100)\/(POS-NEG). EC50 was calculated from a 4-parameter logistic model with the software XLFit (IDBS)."},{"key":"10.1016\/j.bmcl.2018.04.036_h0095","first-page":"4607","volume":"58","author":"Fanjul","year":"2008","journal-title":"Cancer Res"},{"key":"10.1016\/j.bmcl.2018.04.036_h0100","doi-asserted-by":"crossref","first-page":"1008","DOI":"10.1073\/pnas.97.3.1008","volume":"97","author":"Schapira","year":"2000","journal-title":"Proc Natl Acad Sci USA"},{"key":"10.1016\/j.bmcl.2018.04.036_b0065","doi-asserted-by":"crossref","first-page":"4448","DOI":"10.1002\/jps.24676","volume":"104","author":"Poulin","year":"2015","journal-title":"J Pharm Sci"},{"key":"10.1016\/j.bmcl.2018.04.036_b0070","doi-asserted-by":"crossref","first-page":"235","DOI":"10.1517\/17460441003605098","volume":"5","author":"Waring","year":"2010","journal-title":"Expert Opin Drug Discov"},{"key":"10.1016\/j.bmcl.2018.04.036_b0075","unstructured":"Suspension of cryopreserved human hepatocytes was used (pooled from a 10 individuals). Incubations were performed at a test compound concentration of 1 \u00b5M at 37\u00b0C and 5% CO2. The cell density was 0.5\u00d7106 viable cells\/mL. The final DMSO concentration in the incubation is 0.1%. Control incubations were also performed in lysed cells to reveal any non-enzymatic degradation. Two control compounds (phase 1 and 2 metabolism) were included with each species. Samples (65 \u00b5L) were removed from the incubation mixture at 0, 5, 15, 30, 60 and 90 min (control sample at 90min only) and added to acetonitrile:water (75:25), containing internal standard, (175\u00b5L) to stop the reaction. Samples were analyzed by LC-MS\/MS. Half-life and intrinsic clearance were calculated."},{"key":"10.1016\/j.bmcl.2018.04.036_b0080","unstructured":"ChromLogD6.5 was calculated from an HPLC measured Chromatographic Hydrophobicity Index at pH 6.5 using the following equation: ChromLogD6.5 = 0.086\u2217CHI6.5 -3.5. pH 6.5 is used to mimick the more acidic nature of skin. For additional references on CHI, see: Young, R. J.; Green, D. V. S.; Luscombe, C. N.; Hill, A. P. 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