BMS-193885

BMS-193885 is a selective neuropeptide Y1 receptor antagonist (K_i=3.3 nM) that competitively blocks the receptor to inhibit NPY-mediated appetite regulation signaling pathways, reduce food intake and inhibit weight gain. BMS-193885 has good blood-brain barrier penetration and is mainly used in the study of obesity and related metabolic diseases^[1][2][3]. IC50 & Target:Ki: 3.3 nM (Neuropeptide Y₁ receptor)^[1]
IC50: 5.9 nM (hY₁)^[1] In Vitro:Binding assay: BMS-193885 competitively inhibits the binding of ^[125I]Peptide YY to human Y1 receptor in SK-N-MC cell membranes with a Ki value of 3.3 nM for Y1 receptor^[1].
Functional cAMP assay: BMS-193885 (30-3000 nM; 30 min) reverses NPY-induced inhibition of Forskolin (HY-15371)-stimulated cAMP production in CHO cells expressing human Y1 receptor as a competitive antagonist with an apparent Kb of 4.5 nM^[1].
Selectivity analysis: BMS-193885 (10 nM; 1 h) has no significant affinity for other NPY receptors Y2, Y4, and Y5, and is 200-fold less selective for the α1-adrenergic receptor^[1].
In Vivo:Acute feeding suppression: BMS-193885 (30-50 μg/5 μL; i.c.v.; single dose) blocks NPY (5 μg, 10 μg)-induced feeding in satious Sprague-Dawley rats^[1].
Peripheral feeding suppression: BMS-193885 (10 mg/kg; i.p.; single dose) reduces NPY-induced 1-hour food intake and spontaneous nocturnal food intake in male Sprague-Dawley rats^[1][2].
Chronic weight loss: BMS-193885 (10 mg/kg; i.p.; once daily for 44 days) reduces cumulative food intake and weight gain in male Sprague-Dawley rats without tolerance^[1].
Cardiovascular safety: BMS-193885 (30 mg/kg; i.v.; single dose) had no serious adverse effects on heart rate and blood pressure in conscious rats and anesthetized dogs^[1].
BMS-193885 (5 mg/kg; i.p.; single dose) significantly blocked NPY Y1 receptors in Wistar rats and reduced the effects of NPY injection on cardiopulmonary function^[3].