CYM 5520 is a selective and allosteric sphingosine 1-phosphate receptor 2 (S1PR2) agonist with an EC50 of 480nM[1]. CYM 5520 is used in research on S1PR2-mediated bone metabolism/bone regeneration, tumor migration, inflammatory immune regulation, and receptor signaling pathways.
In vitro, CYM 5520 (10μM; 60min) significantly suppressed HGF-induced migration of HuH7 cells[2]. Treatment of HEK293T cells with CYM 5520 (10μM; 2h) induced a marked increase in phospho-ERK1/2 levels (a downstream marker of S1P2 activation)[3].
In vivo, CYM 5520 (10mg/kg; i.p.; 5 days/week; 6 weeks) corrected osteopenia and stimulated osteoblast activity in OVX C57Bl6J mice[4]. CYM 5520 (1mg/kg; i.p.; once daily; 28 days) increased the mRNA expression of osteoblast differentiation markers, including ALP, OPN, BSP, and osteocalcin, in the tibia of 8-week-old male mice[5].
References:
[1]. Satsu, Hideo, et al. "A sphingosine 1-phosphate receptor 2 selective allosteric agonist." Bioorganic & medicinal chemistry 21.17 (2013): 5373-5382.
[2]. Matsushima-Nishiwaki, Rie, et al. "Sphingosine 1-phosphate (S1P) reduces hepatocyte growth factor-induced migration of hepatocellular carcinoma cells via S1P receptor 2." PLoS One 13.12 (2018): e0209050.
[3]. Pitman, Melissa R., et al. "The sphingosine 1-phosphate receptor 2/4 antagonist JTE-013 elicits off-target effects on sphingolipid metabolism." Scientific reports 12.1 (2022): 454.
[4]. Weske, Sarah, et al. "Agonist-induced activation of the S1P receptor 2 constitutes a novel osteoanabolic therapy for the treatment of osteoporosis in mice." Bone 125 (2019): 1-7.
[5]. Matsuzaki, Etsuko, et al. "Sphingosine-1-phosphate receptor 2 agonist induces bone formation in rat apicoectomy and alveolar bone defect model." Journal of Dental Sciences 17.2 (2022): 787-794.