| Size | Price | Stock | Qty |
|---|---|---|---|
| 5mg |
|
||
| 10mg |
|
||
| 50mg |
|
||
| 100mg |
|
||
| Other Sizes |
|
| Targets |
Serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) interaction
|
|---|---|
| ln Vitro |
The quantity of SERT-nNOS complex is considerably reduced when grown 293T cells transfected with nNOS and SERT are incubated with ZZL-7 (1.0 μM) for two hours[1].
|
| ln Vivo |
Two hours after treatment, in vivo electrophysiology in SERT-Cre mice shows a substantial increase in the firing frequency of serotonergic neurons caused by ZZL-7 (10 mg/kg, intraperitoneally). ZZL-7 shortens the duration of immobility in wild-type mice[1]. Two hours after treatment, intragastric injection of ZZL-7 (10, 20, and 40 mg/kg; once) causes dose-dependent antidepressant-like behaviors[1]. Two hours after treatment, chronic unpredictable moderate stress (CMS)-induced depression behaviors are reversed by ZZL-7 (10 mg/kg; intraperitoneal administration)[1].
|
| Enzyme Assay |
Major depressive disorder (MDD) is one of the most common mental disorders. We designed a fast-onset antidepressant that works by disrupting the interaction between the serotonin transporter (SERT) and neuronal nitric oxide synthase (nNOS) in the dorsal raphe nucleus (DRN). Chronic unpredictable mild stress (CMS) selectively increased the SERT-nNOS complex in the DRN in mice. Augmentation of SERT-nNOS interactions in the DRN caused a depression-like phenotype and accounted for the CMS-induced depressive behaviors. Disrupting the SERT-nNOS interaction produced a fast-onset antidepressant effect by enhancing serotonin signaling in forebrain circuits. We discovered a small-molecule compound, ZZL-7, that elicited an antidepressant effect 2 hours after treatment without undesirable side effects. This compound, or analogous reagents, may serve as a new, rapidly acting treatment for MDD [1].
|
| Animal Protocol |
Animal/Disease Models: SERT-Cre mice[1]
Doses: 10 mg/kg Route of Administration: ip; once Experimental Results: Dramatically increased firing frequency of serotonergic neurons 2 hrs (hours) after treatment in vivo electrophysiology in SERT-Cre mice. |
| References |
[1]. Nan Sun, et al. Design of fast-onset antidepressant by dissociating SERT from nNOS in the DRN. Science. 2022 Oct 28;378(6618):390-398.
|
| Molecular Formula |
C11H20N2O4
|
|---|---|
| Molecular Weight |
244.29
|
| Exact Mass |
244.142307
|
| Elemental Analysis |
C, 54.08; H, 8.25; N, 11.47; O, 26.20
|
| CAS # |
99141-91-0
|
| Appearance |
White to off-white oil
|
| LogP |
-0.2
|
| tPSA |
84.5Ų
|
| SMILES |
C(N[C@H](C(N[C@H](C(OC)=O)C(C)C)=O)C)(=O)C
|
| InChi Key |
RHDUVXUSBMPQOK-CBAPKCEASA-N
|
| InChi Code |
InChI=1S/C11H20N2O4/c1-6(2)9(11(16)17-5)13-10(15)7(3)12-8(4)14/h6-7,9H,1-5H3,(H,12,14)(H,13,15)/t7-,9-/m0/s1
|
| Chemical Name |
methyl (2S)-2-[[(2S)-2-acetamidopropanoyl]amino]-3-methylbutanoate
|
| Synonyms |
ZZL-7; ZZL7; ZZL 7
|
| HS Tariff Code |
2934.99.9001
|
| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: This product requires protection from light (avoid light exposure) during transportation and storage. |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
|
| Solubility (In Vitro) |
DMSO: 250 mg/mL (1023.37 mM)
|
|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.51 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (add these co-solvents sequentially from left to right, and one by one), clear solution.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 400 μL PEG300 and mix evenly; then add 50 μL Tween-80 to the above solution and mix evenly; then add 450 μL normal saline to adjust the volume to 1 mL. Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH₂ O to obtain a clear solution. Solubility in Formulation 2: ≥ 2.08 mg/mL (8.51 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), clear solution. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 mg/mL clear DMSO stock solution to 900 μL of 20% SBE-β-CD physiological saline solution and mix evenly. Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. View More
Solubility in Formulation 3: ≥ 2.08 mg/mL (8.51 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 4.0935 mL | 20.4675 mL | 40.9350 mL | |
| 5 mM | 0.8187 mL | 4.0935 mL | 8.1870 mL | |
| 10 mM | 0.4093 mL | 2.0467 mL | 4.0935 mL |
*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.
Calculation results
Working concentration： mg/mL；
Method for preparing DMSO stock solution： mg drug pre-dissolved in μL DMSO (stock solution concentration mg/mL). Please contact us first if the concentration exceeds the DMSO solubility of the batch of drug.
Method for preparing in vivo formulation:：Take μL DMSO stock solution, next add μL PEG300, mix and clarify, next addμL Tween 80, mix and clarify, next add μL ddH2O，mix and clarify.
(1) Please be sure that the solution is clear before the addition of next solvent. Dissolution methods like vortex, ultrasound or warming and heat may be used to aid dissolving.
(2) Be sure to add the solvent(s) in order.
Products are for research use only; We do not sell to patients
Copyright 2020 InvivoChem LLC | All Rights Reserved
