Chemistry:SBP-9330
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| 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 |
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| Formula | C27H24ClNO4 |
| Molar mass | 455.94 g/mol |
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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
- ↑ 1.0 1.1 1.2 "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. January 2011. doi:10.1021/jm1012165. PMID 21155570.
- ↑ "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. 2024.
- ↑ "mGlu2 Receptors in the Basal Ganglia: A New Frontier in Addiction Therapy". Frontiers in Bioscience-Landmark 30 (8). September 2025. doi:10.31083/FBL26637. PMID 40917044.
- ↑ Cosford ND, Panickar DR, Sidique S, Semenova S, Markou A, "Positive allosteric modulators of group II mGluRs", US patent 13051798, issued 2014-06-10, assigned to Sanford Burnham Prebys Medical Discovery Instituteand University of California San Diego UCSD
- ↑ Cosford ND , Sheffler DJ, "Positive allosteric modulator of the metabotropic glutamate receptor subtype 2 receptor, synthesis and solid forms thereof", WO patent 2025019598A1, published 2025-01-23
- ↑ "Preclinical and phase 1 clinical profile of SBP-9330 in development as an aid to smoking cessation". Neuroscience & Biobehavioral Reviews. 2024. 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". https://ctv.veeva.com/study/a-first-in-human-study-of-sbp-9330-in-healthy-subjects.
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