CYM-5478

CYM-5478 is a potent and highly selective S1P₂ agonist with an EC₅₀ of 119?nM in a TGFα-shedding assay. CYM-5478 protects neural-derived cell lines against Cisplatin toxicity^[1][2]. In Vitro: CYM-5478 activates S1P₂ with an EC₅₀ of 119?nM, has less than 25% efficacy and shows 10-fold lower potency against the other S1P receptor subtypes (EC₅₀ of 1690 nM, 1950 nM, >10 μM, >10 μM for S1P₁, S1P₃, S1P₄, S1P₅, respectively)^[1].
CYM-5478 (1, 10, 100, 1000, 10000 nM) induces a statistically significant increase in the viability of C6 cells in a dose dependent manner at concentrations above 100?nM under nutrient-deprivation stress produced by serum-starvation. This effect was absent in the presence of 10% fetal bovine serum^[1].
CYM-5478 (10?μM) causes a statistically significant, 3-fold increase in the EC₅₀ of Cisplatin-mediated reduction in the viability of C6 glioma cells. CYM-5478 also attenuated Cisplatin-induced caspase 3/7 activity^[1].
CYM-5478 (10?μM) causes significantly attenuated the increase of ROS in C6 cells exposed to Cisplatin (20?μM; for 24?hours)^[1].
CYM-5478 (20 μM) protects neural cells but not breast cancer cells against Cisplatin toxicity (C6 glioma cells: EC₅₀=4.54 μM; GT1-7: EC₅₀=17 μM; SK-N-BE2: EC₅₀=7.44 μM; CLU188: EC₅₀=5.54 μM)^[2].
In Vivo: CYM-5478 (1 mg/kg/day; ip) protects against Cisplatin-mediated (3 mg/kg; i.p.; once a week for 3 week) ototoxicity in rats^[2].
CYM-5478 (20 μM) treatment results in near-complete protection from cisplatin-mediated loss of neuromast viability. CYM-5478 protects against loss of hair cell viability in a zebrafish model for ototoxicity^[2].