Retinoic acid receptor (RAR) is a nuclear receptor, which also is a transcription factor. Specifically, RAR has three subtypes: RAR-α, RAR-β, and RAR-γ. Promoter methylation epigenetically regulated the expression of RAR gene. Besides, among its many roles in development, RA determines the identity of differentiated motor neurons by activating RAR-mediated transcription. Moreover,  both RARs and RXRs belong to the steroid hormone/thyroid hormone nuclear receptor superfamily. In the presence of retinoid ligands, RAR (usually heterodimerized with RXR) recruits coactivators (NCOA1 and NCOA2), P300 and core components of the transcription mechanism. In human breast cancer cell lines, FoxA1 is required for RAR recruitment.

Furthermore, RAR mediated the RA signaling pathway. This is very important for many physiological processes such as organ development, regeneration, and differentiation. In invertebrates, RAR interacts with RXR to form different combinations of heterodimers. In addition, ATRα is the main ligand perceived by the RAR-RXR heterodimer in the development process. After binding to ATRα, the RAR-RXR heterodimer regulates transcription by binding to the RA response elements (RAREs) in the regulatory region of the target gene. Here, we will introduce a highly potent RAR agonist, TTNPB.

TTNPB is a Highly Potent RAR Agonist.

First of all, TTNPB is a highly potent RAR agonist. Meanwhile, TTNPB Competitive bindings assays using human RARs yield IC₅₀s of α=5.1 nM, β= 4.5 nM, and γ=9.3 nM, respectively.

In the second place, TTNPB inhibits the binding of [³H]tRA with IC₅₀s of 3.8 nM, 4 nM, and 4.5 nM for human RARα, β, and γ, respectively. Nonetheless, TTNPB competes for [³H]tRA binding to CRABPI with IC₅₀s of 1800 nM.

Last but not the least, the combination of TTNPB+phytol significantly reduced the number of tumors and tumor burden when compared to MNU group of animals treated with TTNPB alone.

All in all, TTNPB is a highly potent RAR agonist.

References:

Pignatello MA, et al. Toxicol Appl Pharmacol. 1997 Feb;142(2):319-27.