Cort108297 is a selective glucocorticoid receptor modulator and a selective GR antagonist with no affinity for other steroid receptors. Cort108297 showed a high affinity for GRs (Ki: 0.45nM).

Cort108297 and CORT118335 had antagonistic effects on dexamethasone-induced KLK3 expression, which were 48% (p<0.05) and 60% (p<0.05), respectively. CORT118335(1µM) inhibited dexamethasone-induced SGK1 expression by 50%. However, Cort108297 was able to completely inhibit dexamethasone-mediated SGK1 elevation (p<0.05). After 3 days of dexamethasone ±SGRMs treatment in CWR-22RV1 cells, the induction effect of SGK1 gene expression was 100 times greater than that in re treated cells, while Cort108297 and CORT118335 completely inhibited this effect (p<0.01). Cort108297 and CORT118335 inhibited 70% and 75% of induction effects, respectively (p<0.01)[1].

At the end of the treatment period, mice treated with Cort108297(40 mg/kg BID) or Cort108297 (80 mg/kg QD) also have significantly lower steady plasma glucose than mice receiving vehicle[3]. Male rats are treated for five days with Mifepristone (10 mg/kg), Cort108297 (30 mg/kg and 60 mg/kg), Imipramine (10mg/kg) or vehicle and exposed to forced swim test (FST) or restraint stress. Experimental data showed that both doses of Cort108297 can effectively inhibit corticosterone response to FST and restraint stress, while only high dose of Cort108297 (60mg/kg) can significantly reduce immobility in forced swimming test (FST). [1].