SBI-553

SBI-553 (also known as SBI-0654553) is a brain-penetrant, orally bioavailable, small-molecule biased positive allosteric modulator (PAM) of neurotensin receptor 1 (NTSR1). It was co-developed by Sanford Burnham Prebys Medical Discovery Institute, Duke University, and the University of Minnesota. SBI-553 binds to an intracellular pocket at the receptor-transducer interface of NTSR1, where it acts as a 'molecular bumper' to block canonical Gq protein coupling while simultaneously acting as a 'molecular glue' to promote beta-arrestin recruitment and alternative G protein coupling (such as Go). Preclinical studies have demonstrated that SBI-553 reduces addictive behaviors associated with psychostimulants (like cocaine and methamphetamine), opioids, and alcohol, and exhibits analgesic properties without inducing the severe thermal (hypothermia) and hemodynamic (hypotension) side effects typically associated with balanced NTSR1 agonists.

Other names

2-{[2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl]-methylamino}ethanol2-[[2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)-1-piperidinyl]-6-quinazolinyl]methylamino]-ethanol