SBP-9330

SBP-9330
Clinical data
Other names	4-chloro-3′-((2-cyclopentyl-1-oxoisoindolin-5-yloxy)methyl)biphenyl-3-carboxylic acid
Routes of; administration	Oral
Drug class	Positive allosteric modulator of mGluR2
Legal status
Legal status	Investigational;
Identifiers
	IUPAC name 4-chloro-3′-((2-cyclopentyl-1-oxoisoindolin-5-yloxy)methyl)biphenyl-3-carboxylic acid;
CAS Number	1260224-86-9 ;
PubChem CID	46182745;
ChemSpider	26389922;
UNII	EH47U5Q8JM;
ChEMBL	ChEMBL1651208;
Chemical and physical data
Formula	C27H24ClNO4
Molar mass	461.94 g·mol−1
3D model (JSmol)	Interactive image;
	SMILES OC(=O)c1cc(ccc1Cl)-c1cccc(COc2ccc3C(=O)N(Cc3c2)C2CCCC2)c1;
	InChI InChI=1S/C27H24ClNO4/c28-24-9-7-22(19-4-2-3-5-20(19)24)18-31-21-6-8-25-23(16-31)27(32)29(26(25)17-21)14-11-12-15-27/h2-9,16,18,21H,11-15,17H2,1H3,(H,32,27); Key:DWTYHCYVKJONSP-UHFFFAOYSA-N;

SBP 9330 is an investigational small-molecule drug and a positive allosteric modulator (PAM) of the metabotropic glutamate receptor 2 (mGluR2), being developed as a potential treatment for nicotine dependence and other substance-use disorders.

Chemistry

SBP 9330 is chemically named 4-chloro-3′-((2-cyclopentyl-1-oxoisoindolin-5-yloxy)methyl)biphenyl-3-carboxylic acid. It consists of a biphenyl-3-carboxylic acid core bearing a chloro substituent and an isoindolinone-derived ether moiety.^[1]

Pharmacology

Pharmacokinetics

Pharmacokinetic analyses showed oral bioavailability, dose-dependent increases in plasma exposure, and parameters compatible with once-daily dosing.^[2]

Pharmacodynamics

SBP 9330 acts as a positive allosteric modulator of mGluR2, a presynaptic G-protein-coupled receptor involved in regulating glutamatergic neurotransmission. Rather than activating the receptor directly, PAMs enhance the receptor's response to endogenous glutamate. Activation of mGluR2 reduces glutamate release in brain regions implicated in reward processing and addiction, including the prefrontal cortex and nucleus accumbens.^[3]

History

SBP 9330 was discovered in medicinal chemistry programs aimed at identifying orally bioavailable mGluR2 PAMs. Early structure–activity relationship studies optimized potency, brain penetration, and pharmacokinetic properties.

It was disclosed in the following patents:

US13051798 – Positive allosteric modulators of group II mGluRs^[4]
WO2025019598A1 – Positive allosteric modulator of the metabotropic glutamate receptor subtype 2 receptor, synthesis and solid forms thereof^[5]

Research

Addiction models

Preclinical studies demonstrated that SBP 9330 decreased cocaine self-administration in rats, suggesting attenuation of drug-reinforcing effects.^[1] Additional experiments within the same paper showed reductions in drug-seeking behavior, attenuation of cue-induced reinstatement, and decreased reward-associated responding.^[1]

Nicotine dependence

SBP 9330 has been evaluated as a potential aid to smoking cessation. In animal models of nicotine reinforcement, mGluR2 positive allosteric modulation was associated with reduced nicotine self-administration and decreased nicotine-seeking behavior.^[6]

Clinical development

Phase I

A randomized, double-blind, placebo-controlled Phase I study evaluated the safety, tolerability, and pharmacokinetics of SBP 9330 following single and multiple ascending oral doses in healthy volunteers.^[7]^[8]

References

1 2 3 Dhanya RP, Sidique S, Sheffler DJ, Nickols HH, Herath A, Yang L, et al. (January 2011). "Design and synthesis of an orally active metabotropic glutamate receptor subtype-2 (mGluR2) positive allosteric modulator (PAM) that decreases cocaine self-administration in rats". Journal of Medicinal Chemistry. 54 (1): 342–353. doi:10.1021/jm1012165. PMC 3071440. PMID 21155570.
↑ Jones A (2024). "Safety, tolerability and pharmacokinetic profile of SBP-9330 in a randomized,double-blind, placebo-controlled Phase 1 clinical trial in healthy nonsmokers and healthy smokers". Society for Research on Nicotine and Tobacco: PPS15–3.
↑ Mao LM, Puthumana E, Wang JQ (September 2025). "mGlu2 Receptors in the Basal Ganglia: A New Frontier in Addiction Therapy". Frontiers in Bioscience-Landmark. 30 (8) 26637. doi:10.31083/FBL26637. PMID 40917044.
↑ US 13051798, Cosford ND, Panickar DR, Sidique S, Semenova S, Markou A, "Positive allosteric modulators of group II mGluRs", issued 2014-06-10, assigned to Sanford Burnham Prebys Medical Discovery Institute and University of California San Diego UCSD
↑ WO 2025019598A1, Cosford ND , Sheffler DJ, "Positive allosteric modulator of the metabotropic glutamate receptor subtype 2 receptor, synthesis and solid forms thereof", published 2025-01-23, assigned to Sanford Burnham Prebys Medical Discovery Institute
↑ Smith J (2024). "Preclinical and phase 1 clinical profile of SBP-9330 in development as an aid to smoking cessation". Neuroscience & Biobehavioral Reviews. doi:10.1016/j.nsa.2024.104106.
↑ Clinical trial number NCT04948827 for "A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Study to Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of SBP-9330 " at ClinicalTrials.gov
↑ "A First-in-Human Study of SBP-9330 in Healthy Subjects". Veeva Clinical Trials.

[Dhanya_2011-1] 1 2 3 Dhanya RP, Sidique S, Sheffler DJ, Nickols HH, Herath A, Yang L, et al. (January 2011). "Design and synthesis of an orally active metabotropic glutamate receptor subtype-2 (mGluR2) positive allosteric modulator (PAM) that decreases cocaine self-administration in rats". Journal of Medicinal Chemistry. 54 (1): 342–353. doi:10.1021/jm1012165. PMC 3071440. PMID 21155570.

[2] Jones A (2024). "Safety, tolerability and pharmacokinetic profile of SBP-9330 in a randomized,double-blind, placebo-controlled Phase 1 clinical trial in healthy nonsmokers and healthy smokers". Society for Research on Nicotine and Tobacco: PPS15–3.

[3] Mao LM, Puthumana E, Wang JQ (September 2025). "mGlu2 Receptors in the Basal Ganglia: A New Frontier in Addiction Therapy". Frontiers in Bioscience-Landmark. 30 (8) 26637. doi:10.31083/FBL26637. PMID 40917044.

[4] US 13051798, Cosford ND, Panickar DR, Sidique S, Semenova S, Markou A, "Positive allosteric modulators of group II mGluRs", issued 2014-06-10, assigned to Sanford Burnham Prebys Medical Discovery Institute and University of California San Diego UCSD

[5] WO 2025019598A1, Cosford ND , Sheffler DJ, "Positive allosteric modulator of the metabotropic glutamate receptor subtype 2 receptor, synthesis and solid forms thereof", published 2025-01-23, assigned to Sanford Burnham Prebys Medical Discovery Institute

[6] Smith J (2024). "Preclinical and phase 1 clinical profile of SBP-9330 in development as an aid to smoking cessation". Neuroscience & Biobehavioral Reviews. doi:10.1016/j.nsa.2024.104106.

[7] Clinical trial number NCT04948827 for "A Randomized, Double-Blind, Placebo-Controlled, First-In-Human Study to Assess Safety, Tolerability, and Pharmacokinetics of Single and Multiple Ascending Doses of SBP-9330 " at ClinicalTrials.gov

[8] "A First-in-Human Study of SBP-9330 in Healthy Subjects". Veeva Clinical Trials.

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