SBI-553

SBI-553
Clinical data
ATC code	None;
Identifiers
	IUPAC name 2-{[2-(1-fluorocyclopropyl)-4-[4-(2-methoxyphenyl)piperidin-1-yl]quinazolin-6-yl]-methylamino}ethanol;
CAS Number	1849603-72-0;
PubChem CID	118610427;
ChemSpider	78316967;
ChEMBL	ChEMBL4576388;
Chemical and physical data
Formula	C26H31FN4O2
Molar mass	450.558 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES CN(CCO)C1=CC2=C(C=C1)N=C(N=C2N3CCC(CC3)C4=CC=CC=C4OC)C5(CC5)F;
	InChI InChI=1S/C26H31FN4O2/c1-30(15-16-32)19-7-8-22-21(17-19)24(29-25(28-22)26(27)11-12-26)31-13-9-18(10-14-31)20-5-3-4-6-23(20)33-2/h3-8,17-18,32H,9-16H2,1-2H3; Key:BLWXTJQMEBQCIZ-UHFFFAOYSA-N;

SBI-553 is an experimental drug which acts as both a β-arrestin biased positive allosteric modulator and also a Gα-biased negative allosteric modulator of the neurotensin receptor NTSR1. It has analgesic effects in animal studies, but importantly also reduces addictive behaviors produced by stimulants and μ-opioid receptor agonists in animal models, suggesting it may be useful as a novel agent for pain relief but which lacks the abuse liability of many currently used analgesic drugs, and may even reduce the potential for addiction when used alongside older analgesics.^[1]^[2]^[3]^[4]

A closely related derivative, SBI-810, has superior analgesic effects and may be more likely to be developed for clinical applications.^[5]^[6]^[7]

References

^ Pinkerton AB, Peddibhotla S, Yamamoto F, Slosky LM, Bai Y, Maloney P, et al. (September 2019). "Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators". Journal of Medicinal Chemistry. 62 (17): 8357–8363. doi:10.1021/acs.jmedchem.9b00340. PMC 7003992. PMID 31390201.
^ Slosky LM, Bai Y, Toth K, Ray C, Rochelle LK, Badea A, et al. (June 2020). "β-Arrestin-Biased Allosteric Modulator of NTSR1 Selectively Attenuates Addictive Behaviors". Cell. 181 (6): 1364–1379.e14. doi:10.1016/j.cell.2020.04.053. PMC 7466280. PMID 32470395.
^ Krumm BE, DiBerto JF, Olsen RH, Kang HJ, Slocum ST, Zhang S, et al. (April 2023). "Neurotensin Receptor Allosterism Revealed in Complex with a Biased Allosteric Modulator". Biochemistry. 62 (7): 1233–1248. doi:10.1021/acs.biochem.3c00029. PMID 36917754.
^ Sun D, Li X, Yuan Q, Wang Y, Shi P, Zhang H, et al. (April 2025). "Molecular mechanism of the arrestin-biased agonism of neurotensin receptor 1 by an intracellular allosteric modulator". Cell Research. 35 (4): 284–295. doi:10.1038/s41422-025-01095-7. PMC 11958688. PMID 40118988.
^ Guo R, Chen O, Zhou Y, Bang S, Chandra S, Li Y, et al. (2025). "Arrestin-biased allosteric modulator of neurotensin receptor 1 alleviates acute and chronic pain". Cell. doi:10.1016/j.cell.2025.04.038. PMID 40393456.
^ Kirkendoll SM (19 May 2025). "Experimental Painkiller Could Outsmart Opioids – Without the High". Duke University School of Medicine.
^ "Non-Opioid Compound Shows Acute and Chronic Pain Relief Potential". Inside Precision Medicine. 20 May 2025.

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[1] Pinkerton AB, Peddibhotla S, Yamamoto F, Slosky LM, Bai Y, Maloney P, et al. (September 2019). "Discovery of β-Arrestin Biased, Orally Bioavailable, and CNS Penetrant Neurotensin Receptor 1 (NTR1) Allosteric Modulators". Journal of Medicinal Chemistry. 62 (17): 8357–8363. doi:10.1021/acs.jmedchem.9b00340. PMC 7003992. PMID 31390201.

[2] Slosky LM, Bai Y, Toth K, Ray C, Rochelle LK, Badea A, et al. (June 2020). "β-Arrestin-Biased Allosteric Modulator of NTSR1 Selectively Attenuates Addictive Behaviors". Cell. 181 (6): 1364–1379.e14. doi:10.1016/j.cell.2020.04.053. PMC 7466280. PMID 32470395.

[3] Krumm BE, DiBerto JF, Olsen RH, Kang HJ, Slocum ST, Zhang S, et al. (April 2023). "Neurotensin Receptor Allosterism Revealed in Complex with a Biased Allosteric Modulator". Biochemistry. 62 (7): 1233–1248. doi:10.1021/acs.biochem.3c00029. PMID 36917754.

[4] Sun D, Li X, Yuan Q, Wang Y, Shi P, Zhang H, et al. (April 2025). "Molecular mechanism of the arrestin-biased agonism of neurotensin receptor 1 by an intracellular allosteric modulator". Cell Research. 35 (4): 284–295. doi:10.1038/s41422-025-01095-7. PMC 11958688. PMID 40118988.

[5] Guo R, Chen O, Zhou Y, Bang S, Chandra S, Li Y, et al. (2025). "Arrestin-biased allosteric modulator of neurotensin receptor 1 alleviates acute and chronic pain". Cell. doi:10.1016/j.cell.2025.04.038. PMID 40393456.

[6] Kirkendoll SM (19 May 2025). "Experimental Painkiller Could Outsmart Opioids – Without the High". Duke University School of Medicine.

[7] "Non-Opioid Compound Shows Acute and Chronic Pain Relief Potential". Inside Precision Medicine. 20 May 2025.

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