The nuclear retinoic acid receptors (RARs) are transcriptional transregulators, and belong to the family of nuclear receptors. RARs consist of three subtypes, α (NR1B1), β (NR1B2), and γ (NR1B3), encoded by separate genes. RARs function as ligand-dependent transcriptional regulators, heterodimerized with retinoid X receptors (RXRs), and bind the cis-acting retinoic acid response elements (RAREs). RXRs also consist of three types, α NR2B1, β (NR2B2), and γ (NR2B3). RARs play critical roles in a variety of biological processes, including development, reproduction, immunity, organogenesis, and homeostasis.

Retinoic acid receptor gamma (RARγ), also known as NR1B3 (nuclear receptor subfamily 1, group B, member 3). RARγ is an important regulator of cartilage development and growth. Ablation of RARγ is associated with reduced chondrocyte proliferation and decreased expression and deposition of proteoglycans. Therefore, RARγ null mice exhibit growth deficiency. Stimulation of RARγ action by retinoid agonists can inhibit heterotopic ossification in various types of animal models. In addition, stimulation of RARγ suppresses chondrogenesis and osteochondroma formation in MHE mouse models via BMP signaling inhibition. RARγ is the principal receptor that functions in RA-mediated growth arrest in keratinocytes. RARγ mediates the anti-proliferative and apoptotic effects of retinoids in certain tissues and cancer cells, such as melanoma and neuroblastoma cells.

BMS961 is a selective RARγ agonist.

BMS961 is a potent and selective RARγ agonist. And BMS961 displays no activity at RARα receptors. BMS961 is detrimental to limb chondrogenesis and growth of CD-1 mice at embryonic stage. In addition, BMS961 treatment limbs exhibit a significant upregulation of two genes: Mgp and Gdf10. Meanwhile, BMS961 inhibits the Dectin-1 expression and pro-inflammatory cytokines production induced by aspergillus fumigatus in human corneal epithelial cells. BMS961 plays an anti-inflammatory role in innate immune responses against A. fumigatus.

All in all, BMS961, a potent and selective RARγ agonist, shows anti-inflammatory activity.


Garcia SA. Int J Mol Sci. 2020 Apr 13;21(8):2686.