SBI-810 is a blood-brain barrier-permeable NTSR1 modulator. SBI-810 promotes the recruitment of β-arrestin-2 to NTSR1 and antagonizes NTSR1-mediated Gq activation. SBI-810 inhibits excitatory synaptic transmission, NMDA receptor and extracellular signal-regulated kinase (ERK) signaling in spinal nociceptive neurons, reduces surface expression of Nav1.7 and action potential firing in primary sensory neurons, and attenuates C-fiber responses. SBI-810 effectively alleviates acute and chronic pain in various rodent models through peripheral and central modulation. SBI-810 is applicable to research related to multiple pain disorders[1][2].
In Vitro, SBI-810 (10 min) stimulates the recruitment of β-arrestin 2 to human NTSR1 in HEK293T cells, and antagonizes Gq activation induced by Neurotensin (NT)[1].
Bath-applied SBI-810 (5 μM, administered during recording) decreases the action potential firing frequency of DRG neurons, increases their rheobase, and inhibits neuronal excitability[1].
In Vivo, SBI-810 (12 mg/kg/10 µg~22 nmol); 1 µg; i.p./i.t.; single dose) exerts potent, NTSR1- and βarr2-dependent spinal analgesic effects in naive C57BL/6J mice, and alleviates physiological acute mechanical and thermal pain[1].
SBI-810 (20 µg; i.t.; single dose) exerts potent analgesic effects on physiological acute mechanical pain in naive Sprague Dawley rats[1].
SBI-810 (12 mg/kg; i.p.; single dose) potently inhibits pain in mouse plantar incision and tibial fracture post-surgical pain models[1].
SBI-810 (12 mg/kg/10 µg; i.p./i.t.; single dose, administered 7 days post-surgery) exerts potent, NTSR1- and βarr2-dependent analgesic effects in SNI model mice, alleviating neuropathic mechanical allodynia and cold allodynia[1].
SBI-810 (12 mg/kg; i.p.; single dose; administered concurrently with formalin injection) potently inhibits inflammatory hyperalgesia and mechanical allodynia, and reduces formalin-induced activation of nociceptors in DRG neurons in mouse formalin/CFA inflammatory pain models[1].
SBI-810 (12 mg/kg; i.p.; single dose; administered post-STZ-induced hyperglycemia) potently alleviates mechanical pain and cold pain in mice with STZ-induced diabetic neuropathic pain[1].
SBI-810 (12-30 mg/kg; i.p.; single dose) attenuates or abolishes morphine-induced CPP, and significantly reduces the cumulative withdrawal score induced by Naloxone in mice treated with escalating doses of morphine[1].
References:
[1]. Guo R, et al. Arrestin-biased allosteric modulator of neurotensin receptor 1 alleviates acute and chronic pain. Cell. 2025;188(16):4332-4349.e21.
[2]. Pottie E, et al. Pain management beyond opioids: a β-arrestin2-biased allosteric GPCR modulator opens new avenues for drug development. Signal Transduct Target Ther. 2025 Aug 27;10(1):264.