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Chemical Structure| 99141-91-0 Chemical Structure| 99141-91-0

Structure of ZZL-7
CAS No.: 99141-91-0

Chemical Structure| 99141-91-0

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ZZL-7 is a rapid-acting antidepressant that works by disrupting the interaction between serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN). ZZL-7 easily crosses the blood-brain barrier and can be used in research on major depressive disorder (MDD).

4.5 *For Research Use Only !

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Product Citations

Product Citations

Chen, Yu-qi ; Ye, Jun-rui ; Wang, Sha-sha ; Peng, Ye ; Zhou, Run ; Yuan, Ruo-lan , et al.

Abstract: Selective serotonin reuptake inhibitors (SSRIs) are characterized by delayed therapeutic onset largely due to their reliance on the desensitization of 5-HT1A autoreceptors (5-HT1ARautos) within the dorsal raphe nucleus (DRN). It has been shown that dissociation of serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) interaction selectively modulates 5-HT1ARautos, thereby facilitating fast-onset antidepressant responses. Targeting the atypical disk large/ZO-1 (PDZ) domain has been implicated in the SERT-nNOS interaction. In this study, we established a drug screening system based on mBRET combined with biological tests to find SERT-nNOS interaction blockers (SNIBs). During screening the compound libraries, 9 top candidates were found to be capable of binding to the PDZ domain of nNOS. We then identified esflurbiprofen as a promising fast-onset antidepressant candidate. Pharmacodynamic studies revealed that esflurbiprofen effectively penetrated the DRN following systemic administration. Esflurbiprofen (10, 20, 40 mg/kg, i.p., once every 4 days) dose-dependently ameliorated depressive-like behaviors in mice subjected to chronic social defeat stress (CSDS) and chronic restraint stress (CRS). In rs-fMRI analysis, we found that esflurbiprofen enhanced the functional connectivity of emotion-related neural networks in CSDS mice. We further demonstrated that esflurbiprofen disrupted the SERT-nNOS complex in the DRN, augmented membrane-associated SERT, and reduced the concentration of 5-HT in the extracellular space of the DRN. This cascade subsequently enhanced serotonergic neuronal firing through the inhibition of negative feedback mediated by 5-HT1ARautos, culminating in an augmented release of 5-HT from serotonergic neurons projecting to the prefrontal cortex and hippocampus. These results highlight the potential of esflurbiprofen to induce rapid antidepressant effects by targeting the SERT-nNOS interaction within the DRN.

Keywords: depression ; fast-onset antidepressant ; esflurbiprofen ; serotonin transporter ; neuronal nitric oxide synthase ; dosal raphe nucleus

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Product Details of ZZL-7

CAS No. :99141-91-0
Formula : C11H20N2O4
M.W : 244.29
SMILES Code : CC(N[C@@H](C)C(N[C@@H](C(C)C)C(OC)=O)=O)=O
MDL No. :MFCD34676342

Safety of ZZL-7

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H302-H315-H319
Precautionary Statements:P501-P270-P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313-P301+P312+P330

Isoform Comparison

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

4.09mL

0.82mL

0.41mL

20.47mL

4.09mL

2.05mL

40.93mL

8.19mL

4.09mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2
 

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