Discovery of novel retinoic acid receptor agonists having potent antiproliferative activity in cervical cancer cells.
Retinoic acid receptor (RAR) active retinoids have proven therapeutically useful for treating certain cancers and dermatological diseases. Herein, we describe the discovery of two new RAR active trienoic acid retinoids, (2E,4E,6E)-7-(3,5-di-tert-butylphenyl)-3-methylocta-2, 4,6-trienoic acid (10a, ALRT1550) and (2E,4E,6Z)-7-(3,5-di-tert-butylphenyl)-3-methylocta-2, 4,6-trienoic acid (10b, LG100567). ALRT1550 is a RAR selective retinoid which exhibits exceptional potency in both competitive binding and cotransfection assays. Moreover, it is the most potent antiproliferative retinoid described to date and thus has implications for the treatment of certain cancers. LG100567 is a potent panagonist which activates both RARs and retinoid X receptors.
Zhang
L
L
Department of Retinoid Chemistry, Ligand Pharmaceuticals, Inc., San Diego, California 92121, USA.
Nadzan
A M
AM
Heyman
R A
RA
Love
D L
DL
Mais
D E
DE
Croston
G
G
Lamph
W W
WW
Boehm
M F
MF
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D015394:Molecular Structure; D018168:Receptors, Retinoic Acid / Q000819:agonists* / Q000378:metabolism; D047488:Retinoid X Receptors; D012176:Retinoids / Q000737:chemistry / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014407:Tumor Cells, Cultured; D002583:Uterine Cervical Neoplasms
D000970:Antineoplastic Agents; D018168:Receptors, Retinoic Acid; D047488:Retinoid X Receptors; D012176:Retinoids; D014157:Transcription Factors; C100800:ALRT 1550; D013936:Thymidine