180713-37-5

LG 100754 is a ligand of retinoid X receptor (RXR) that modulates the activity of RXR dimers. It acts as an antagonist towards RXR homodimers but as an agonist of heterodimers consisting of RXR and retinoic acid receptor (RAR) or PPARs. LG 100754, at 1 μM, is a weak agonist of RXR-PPARγ but strongly enhances signaling through the heterodimer in response to PPARγ ligands, including rosiglitazone and 15-deoxy-Δ^12,14-prostaglandin J₂ . Through this action, LG 100754 decreases glucose levels and relieves insulin resistance in mice.

LG 100754 is a novel RXR:PPARγ agonist and decreases glucose levels in vivo. It can also be used in compositions comprising anti-androgen and anti-thyroid agents and kits for diagnosis and treatment of viral respiratory infection.

PPARα; PPARγ

[1] TAKAYUKI HIDA . Existence of Retinoic Acid-Receptor-Independent Retinoid X-Receptor-Dependent Pathway in Myeloid Cell Function[J]. Japanese journal of pharmacology, 2001, 85 1: 60-69. DOI: 10.1254/jjp.85.60
[2] DEEPAK S. LALA. Activation of specific RXR heterodimers by an antagonist of RXR homodimers[J]. Nature, 1996, 383 6599: 450-453. DOI: 10.1038/383450a0
[3] I G SCHULMAN. The phantom ligand effect: allosteric control of transcription by the retinoid X receptor.[J]. Genes & development, 1997, 11 3: 299-308. DOI: 10.1101/gad.11.3.299
[4] FORMAN B M. The Antidiabetic Agent LG100754 Sensitizes Cells to Low Concentrations of Peroxisome Proliferator-activated Receptor γ Ligands*[J]. The Journal of Biological Chemistry, 2002, 20 1: 12503-12506. DOI: 10.1074/jbc.c200004200
[5] R. CESARIO. The rexinoid LG100754 is a novel RXR:PPARgamma agonist and decreases glucose levels in vivo.[J]. Molecular endocrinology, 2001, 15 8 1: 1360-1369. DOI: 10.1210/mend.15.8.0677