Retinoic acid receptor ligands based on the 6-cyclopropyl-2,4-hexadienoic acid.
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.
Farmer
Luc J
LJ
Discovery Research, Ligand Pharmaceuticals, Inc., 10275 Science Center Drive, San Diego, CA 92121, USA. farmer@vpharm.com
Zhi
Lin
L
Jeong
Susan
S
Lamph
William W
WW
Osburn
Deborah L
DL
Croston
Glenn
G
Flatten
Karen S
KS
Heyman
Rich A
RA
Nadzan
Alex M
AM
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
D003521:Cyclopropanes; D007202:Indicators and Reagents; D008024:Ligands; D018168:Receptors, Retinoic Acid; D013011:Sorbic Acid