R121919 (NBI30775) is a potent small molecule antagonist of the adrenocorticotropic hormone-releasing factor receptor 1 (CRF1), demonstrating antidepressant and anxiolytic activity, and inhibiting the CRF1 receptor, CRF2 receptor, and CRF-binding proteins.

CRF1 receptor:2-5 nM (Ki)

R121919 is a potent small-molecule CRF1 receptor antagonist, exhibiting high affinity for the CRF1 receptor with a Ki value in the range of 2–5 nM. Notably, its activity at the CRF2 receptor, CRF-binding protein, and 70 other receptor types is over 1000-fold weaker[2].

In rats, R121919 demonstrates a dose-dependent reduction in adrenocorticotropic hormone and corticosterone responses to restraint stress. At a dose of 10 mg/kg R121919, peak plasma concentrations of adrenocorticotropic hormone and corticosterone are decreased by 9% and 25%, respectively[2].
Moreover, R121919 exhibits anxiolytic effects in mice with a steep dose-response curve, leading to reduced anxiety levels. Some of the intracellular targets of the drug include molecules like GR (glucocorticoid receptor), MR (mineralocorticoid receptor), BAG-1 (Bcl-2-associated athanogene-1), and AP-1 (activator protein 1)[1].