MSU-42011 is an orally active retinoid X receptor (RXR) agonist. MSU-42011 inhibits the iNOS activity and reduces the expression of p-ERK protein. MSU-42011 has immunomodulatory and antitumor activity.
MSU-42011 (0-1 μM) inhibits iNOS with an IC50 of 158 nM in RAW264.7 macrophage-like cells[1].MSU-42011 (300 nM; 8 h) shows a low induction effect on SREBP in HepG2 cells[1].MSU-42011 (0-5000 nM; 24 h) can activate RXRα in HepG2 cells[1].
MSU-42011 (25 mg/kg, PO, for 12 weeks) significantly reduces the number, size and overall tumor burden of tumors in an A/J mouse lung cancer model.Fewer cells actively proliferated and showed a significant [1] reduction in p-ERK compared to controls.MSU-42011 (25 mg/kg; PO; 1 week later, intraperitoneal injection of Carboplatin (50 mg/kg) and paclitaxel (15 mg/kg) every other week 6 times; treatment for 12 weeks) is most effective in reducing tumor number, tumor size, and overall tumor burden when combined with C/P in the A/J mouse lung cancer model.Decreased macrophages in the lung and increases CD8+ T cell activation markers[1].MSU42011 (100 mg/kg; PO; 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[2].
References:
[1]. Moerland JA, et al. The novel rexinoid MSU-42011 is effective for the treatment of preclinical Kras-driven lung cancer. Sci Rep. 2020 Dec 17;10(1):22244.
[2]. Ana S Leal, et al. The RXR Agonist MSU42011 Is Effective for the Treatment of Preclinical HER2+ Breast Cancer and Kras-Driven Lung Cancer. Cancers (Basel). 2021 Oct 6;13(19):5004.