GAT100

GAT100 is a negative allosteric modulator and covalent allosteric probe for cannabinoid receptor type 1 (CB1R). GAT100 acts as a positive allosteric modulator for orthosteric agonist CP55,940 binding to regulate the CB1R signaling pathway. GAT100 reduces the potency and efficacy of orthosteric CB1R agonists in terms of β-arrestin 1 recruitment, phosphorylation of PLCβ3 and ERK1/2, cAMP accumulation, and CB1R internalization. GAT100 is applicable to the research of psychobehavioral and somatic diseases^[1][2]. In Vitro:GAT100 (Compound 20) (30 min preincubation, 90 min co-incubation with CP55,940) potently inhibits CP55,940-dependent β-arrestin recruitment and cAMP accumulation in CHO-K1 hCB1R cells, with EC₅₀ values of 2.09 nM and 174 nM, respectively^[1].
GAT100 (treated at 37 °C for 60 minutes) acts as a positive allosteric modulator of [³H]CP55,940 binding to CHO hCB1R membranes, with an EC₅₀ of 19.6 nM^[1].
GAT100 (500 nM; 0-120 min) covalently labels hCB1R in the cell membrane of HEK293 cells in a time-dependent manner and forms a covalent bond with hCB1R^[1].
GAT100 (30 min) potently inhibits CB1-mediated β-arrestin1 recruitment, PLCβ3 phosphorylation, and ERK1/2 phosphorylation in HEK293A, Neuro2a, and STHdhQ7/Q7 cells^[2].
GAT100 (1-10000 nM; 4 h) potently inhibits CB1-mediated, forskolin-stimulated cAMP accumulation in HEK-CRE cells^[2].
GAT100 (1 μM; 0.5-20 h) rapidly reverses CP55,940-induced CB1 endocytosis in STHdhQ7/Q7 cells, and it restores plasma membrane CB1 levels more rapidly than the reference allosteric modulator^[2].