This paper describes Targretin (LGD1069) as well as more potent analogs (LGD1268):
J Med Chem 1995 Aug 4;38(16):3146-3155
Design and synthesis of potent retinoid X receptor selective
ligands that induce apoptosis in leukemia cells.
Boehm MF, Zhang L, Zhi L, McClurg MR, Berger E, Wagoner M, Mais DE, Suto CM,
Davies JA, Heyman RA, et al
Department of Retinoid Chemistry Research, Ligand Pharmaceuticals, Inc., San Diego, California
92121, USA.
Structural modifications of the retinoid X receptor (RXR) selective compound
4-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydro-2- naphthyl)ethenyl]benzoic acid (LGD1069),
which is currently in phase I/IIA clinical trials for cancer and dermatological indications, have
resulted in the identification of increasingly potent retinoids with > 1000-fold selectivity for the
RXRs. This paper describes the design and preparation of a series of RXR selective retinoids as
well as the biological data obtained from cotransfection and competitive binding assays which were
used to evaluate their potency and selectivity. The most potent and selective of the analogs is
6-[1-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2- yl)cyclopropyl]nicotinic acid (12d;
LG100268). This compound has proven useful for investigating RXR dependent biological
pathways including the induction of programmed cell death (PCD) and transglutaminase (TGase)
activity. Our studies indicate that the induction of PCD and TGase in human leukemic myeloid cells
is dependent upon activation of RXR-mediated pathways.
PMID: 7636877, UI: 95363839 |
