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9-cis-Retinoic acid activates all isoforms of the retinoic acid receptor (RAR) (Ki = 0.5-27 nM) as well as retinoid X receptor (RXR) isoforms (Ki = 3.8-12 nM) (Umemiya et al.; Wong et al.). The ability of RAR to heterodimerize with RXR, and the latter to heterodimerize with other partners allows 9-cis-retinoic acid to evoke a wide range of effects (Dawson et al.; Kane).
DIFFERENTIATION
· Increases the number of neurons derived from rat neural stem cell cultures (Laeng et al.).
· Promotes oligodendrocyte precursor cell differentiation and myelination in cultured cells and mouse cerebellar slices (Huang et al.).
· Induces formation of pancreatic ducts, but not acini, in embryonic mouse pancreas grown in collagen gel (Kadison et al.; Kobayashi et al.).
· Enhances BMP9-induced osteogenic differentiation of mesenchymal progenitor cells, in vitro and in vivo (Zhang et al.).
· Induces myogenic differentiation of C2C12 myoblast progenitor cells (Zhu et al.).
CANCER RESEARCH
· Inhibits proliferation of Epstein-Barr virus-infected lymphoblastoid cell lines (Pomponi et al.).
· Inhibits growth of cultured human gastric cancer cells (Naka et al.).
· Inhibits spontaneous proliferation and CD40-induced growth in primary mantle cell lymphoma cells (Guidoboni et al.).
Cell Type
Cancer Cells and Cell Lines, Leukemia/Lymphoma Cells, Mesenchymal Stem and Progenitor Cells, Myogenic Stem and Progenitor Cells, Neural Stem and Progenitor Cells, Osteoblasts, Pancreatic Cells
This product is designed for use in the following research area(s) as part
of the highlighted workflow stage(s). Explore these workflows to learn more about the other products we
offer to support each research area.
Analysis, occurrence, and function of 9-cis-retinoic acid.
Kane MA
Biochimica et biophysica acta 2012 JAN
Abstract
Metabolic conversion of vitamin A (retinol) into retinoic acid (RA) controls numerous physiological processes. 9-cis-retinoic acid (9cRA), an active metabolite of vitamin A, is a high affinity ligand for retinoid X receptor (RXR) and also activates retinoic acid receptor (RAR). Despite the identification of candidate enzymes that produce 9cRA and the importance of RXRs as established by knockout experiments, in vivo detection of 9cRA in tissue was elusive until recently when 9cRA was identified as an endogenous pancreas retinoid by validated liquid chromatography-tandem mass spectrometry (LC-MS/MS) methodology. This review will discuss the current status of the analysis, occurrence, and function of 9cRA. Understanding both the nuclear receptor-mediated and non-genomic mechanisms of 9cRA will aid in the elucidation of disease physiology and possibly lead to the development of new retinoid-based therapeutics. This article is part of a Special Issue entitled Retinoid and Lipid Metabolism.
The retinoid X receptors and their ligands.
Dawson MI and Xia Z
Biochimica et biophysica acta 2012 JAN
Abstract
This chapter presents an overview of the current status of studies on the structural and molecular biology of the retinoid X receptor subtypes α, β, and γ (RXRs, NR2B1-3), their nuclear and cytoplasmic functions, post-transcriptional processing, and recently reported ligands. Points of interest are the different changes in the ligand-binding pocket induced by variously shaped agonists, the communication of the ligand-bound pocket with the coactivator binding surface and the heterodimerization interface, and recently identified ligands that are natural products, those that function as environmental toxins or drugs that had been originally designed to interact with other targets, as well as those that were deliberately designed as RXR-selective transcriptional agonists, synergists, or antagonists. Of these synthetic ligands, the general trend in design appears to be away from fully aromatic rigid structures to those containing partial elements of the flexible tetraene side chain of 9-cis-retinoic acid. This article is part of a Special Issue entitled Advances in High Density Lipoprotein Formation and Metabolism: A Tribute to John F. Oram (1945-2010).
Retinoid X receptor gamma signaling accelerates CNS remyelination.
Huang JK et al.
Nature neuroscience 2011 JAN
Abstract
The molecular basis of CNS myelin regeneration (remyelination) is poorly understood. We generated a comprehensive transcriptional profile of the separate stages of spontaneous remyelination that follow focal demyelination in the rat CNS and found that transcripts that encode the retinoid acid receptor RXR-γ were differentially expressed during remyelination. Cells of the oligodendrocyte lineage expressed RXR-γ in rat tissues that were undergoing remyelination and in active and remyelinated multiple sclerosis lesions. Knockdown of RXR-γ by RNA interference or RXR-specific antagonists severely inhibited oligodendrocyte differentiation in culture. In mice that lacked RXR-γ, adult oligodendrocyte precursor cells efficiently repopulated lesions after demyelination, but showed delayed differentiation into mature oligodendrocytes. Administration of the RXR agonist 9-cis-retinoic acid to demyelinated cerebellar slice cultures and to aged rats after demyelination caused an increase in remyelinated axons. Our results indicate that RXR-γ is a positive regulator of endogenous oligodendrocyte precursor cell differentiation and remyelination and might be a pharmacological target for regenerative therapy in the CNS.
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