title: Retinoic acid receptor ligands based on the 6-cyclopropyl-2,4-hexadienoic acid.
abstract: A series of novel cyclopropanyl methyl hexadienoic acid retinoids was designed and prepared. These compounds exhibited either selective activity as RXR agonists or pan-agonists on one or more of each of the RAR and RXR isoforms. The most potent pan-agonist 5a (RAR's EC(50)=17-59 nM; RXR's EC(50)=6-14 nM) showed good antiproliferative properties in the in vitro cancer cell lines, ME 180 and RPMI 8226.
authors.affiliation: Discovery Research, Ligand Pharmaceuticals, Inc., 10275 Science Center Drive, San Diego, CA 92121, USA. farmer@vpharm.com
authors.forename: Luc J
authors.initials: LJ
authors.lastname: Farmer
authors.forename: Lin
authors.initials: L
authors.lastname: Zhi
authors.forename: Susan
authors.initials: S
authors.lastname: Jeong
authors.forename: William W
authors.initials: WW
authors.lastname: Lamph
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Osburn
authors.forename: Glenn
authors.initials: G
authors.lastname: Croston
authors.forename: Karen S
authors.initials: KS
authors.lastname: Flatten
authors.forename: Rich A
authors.initials: RA
authors.lastname: Heyman
authors.forename: Alex M
authors.initials: AM
authors.lastname: Nadzan
mesh_terms: D001667:Binding, Competitive / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D003521:Cyclopropanes / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D008024:Ligands; D018168:Receptors, Retinoic Acid / Q000819:agonists / Q000187:drug effects* / Q000235:genetics; D013011:Sorbic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D014162:Transfection; D014407:Tumor Cells, Cultured
chemical_list: D003521:Cyclopropanes; D007202:Indicators and Reagents; D008024:Ligands; D018168:Receptors, Retinoic Acid; D013011:Sorbic Acid