The retinoid X receptor (RXR) belongs to the nuclear receptor superfamily. The nuclear receptors superfamily has many other nuclear receptors, including the retinoic acid receptor (RAR), vitamin D receptor (VDR), peroxisome proliferator-activated receptor (PPAR), or liver X receptor (LXR). RXR homodimerizes or heterodimerizes with other nuclear receptors, and upon ligand binding, the dimers act as transcription factors, regulating genes involved in inflammation, cell proliferation or differentiation, and apoptosis. This profile makes RXR an attractive target for anti-cancer therapies. Today, we will introduce an effective RXR agonist — MSU42011. It can be used for the research of kinds of cancers, such as preclinical HER2+ breast cancer and kras-driven lung cancer.
MSU-42011 is an orally active and effective RXR agonist for cancer research.
MSU-42011 is an orally active RXR agonist with immunomodulatory and antitumor activity. In vitro, MSU-42011 inhibits the expression of iNOS and p-ERK protein.
In vivo, Firstly, MSU-42011 (25 mg/kg, p.o., for 12 weeks) significantly reduces the number, size and overall tumor burden of tumors in an A/J mouse lung cancer model. Secondly, fewer cells actively proliferated and showed a significant reduction in p-ERK compared to controls. Meanwhile, MSU-42011 (25 mg/kg; p.o.; 1 week later, intraperitoneal injection of 50 mg/kg Carboplatin and 15 mg/kg Paclitaxel every other week 6 times, for 12 weeks) reduce tumor number, tumor size, and overall tumor burden. Furthermore, MSU-42011decreases macrophages in the lung and increases CD8+ T cell activation markers when combined with C/P in the A/J mouse lung cancer model. Finally, MSU42011 (100 mg/kg; p.o.; 2 weeks later, intraperitoneal injection 50mg/mouse of anti-PD1 and anti-PDL1 antibodies, twice a week, a total of 22 times) reduces tumor burden in a mouse lung tumor model.
All in all, MSU-42011 is an RXR agonist for cancer research.
Reference:
[1] Moerland JA, et al. Sci Rep. 2020 Dec 17;10(1):22244.
[2] Leal AS, et al. 2021 Oct 6;13(19):5004.