SBI-553 is a β-arrestin-biased positive allosteric modulator (PAM) of neurotensin receptor 1 (NTSR1).1 It binds to NSTR1 and increases neurotensin-1 affinity for NSTR1 in HEK293 cells expressing the human receptor when used at concentrations ranging from 0.01 to 10 ?M. SBI-553 (0.03-30 ?M) induces β-arrestin recruitment and NTSR1 internalization without stimulating Gq protein activation, 1,4,5-triphosphate (IP3) generation, or calcium mobilization in cell-based assays. In vivo, SBI-553 (12 mg/kg, i.p.) attenuates cocaine- or methamphetamine-induced hyperlocomotion in wild-type but not β-arrestin-2 knockout mice. It also reduces cocaine self-administration in mice.
1.Slosky, L.M., Bai, Y., Toth, K., et al.β-Arrestin-biased allosteric modulator of NTSR1 selectively attenuates addictive behaviorsCell181(6)1364-1379.e1314(2020)