| Size | Price | Stock | Qty |
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| Targets |
UNC9995 targets the dopamine D2 receptor (Drd2) as a β-arrestin-2-biased agonist. It preferentially activates β-arrestin-2-dependent signaling with an EC50 of 120 nM and an Emax of 88%. The compound exhibits negligible activity at canonical Gαi protein-mediated pathways. It enhances the interaction of β-arrestin2 with NLRP3, thereby reducing IL-1β production.
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| ln Vitro |
After induction with IL-6 (300 ng/mL; 24 hours), UNC9995 (10 μM; 1 hour) restores primary astrocyte astrocytes and improves the binding of STAT3 and β-arrestin2. Additionally, it suppresses STING UNC9995 (1, 5, 10, and 20 μM; 1 hour), which when activated with IL-6 (300 ng/mL; 24 hours) can completely eradicate cellular inflammation as well as WT and Arrb2, TBK1, JAK [1].
UNC9995 is a β-arrestin-2-biased agonist of the dopamine D2 receptor with an EC50 of 120 nM and Emax of 88% for β-arrestin recruitment. It inhibits NLRP3 inflammasome activation by enhancing β-arrestin2-NLRP3 interaction. The compound prevents neuronal degeneration and reduces IL-1β production. It has been deployed as a chemical probe to dissect β-arrestin-2-dependent neuroinflammatory mechanisms. |
| ln Vivo |
In mice and rats, UNC9995 (2 mg/kg/day, i.p., for two weeks) ameliorates depressive-like behavioral phenotypes in the chronic unpredictable indoor (CUMS) and chronic social defeat daytime (CSDS) models.
In vivo activity data for UNC9995 are limited in the available literature. The compound is used in preclinical models of Parkinson's disease and major depressive disorder to study β-arrestin-2-dependent neuroinflammatory mechanisms. It inhibits NLRP3 inflammasome activation and JAK/STAT3 pathway suppression. The compound prevents neuronal degeneration in Parkinson's disease models via a β-arrestin2-biased mechanism. |
| Enzyme Assay |
Specific cell-free enzyme/receptor binding assay protocols for UNC9995 involve β-arrestin recruitment assays. The compound’s EC50 of 120 nM and Emax of 88% for β-arrestin-2 recruitment are determined using cell-based reporter systems. Gαi protein-mediated pathway activation is assessed to confirm negligible activity. Receptor binding affinity is evaluated using radioligand displacement assays.
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| Cell Assay |
Western Blot analysis [1]
Cell Types: primary astrocytes Tested Concentrations: 10 μM Incubation Duration: pre-incubation 1 h; -/− post-astrocytes [1]. Results of using 300 ng/mL IL-6: Enhanced interaction between STAT3 and β-arrestin2. Eliminate the activation of cGAS-STING and JAK/STAT3 pathways stimulated by IL-6, and reduce the levels of p-STING, p-TBK1, and p-JAK. In vitro cell-based assays for UNC9995 use cells expressing the dopamine D2 receptor. β-arrestin-2 recruitment is measured using BRET or similar assays to determine EC50 (120 nM) and Emax (88%). NLRP3 inflammasome activation is assessed by measuring IL-1β production. The compound’s ability to enhance β-arrestin2-NLRP3 interaction is confirmed by co-immunoprecipitation. |
| Animal Protocol |
Animal/Disease Models: Chronic Unpredictable Mild Stress (CUMS) Mouse Model[1]
Doses: 2 mg/kg/d Route of Administration: IP; improves the loss of star-shaped astrocytes in the hippocampus[1]. 2-week Experimental Results: Depressive-like symptoms of the CUMS mouse model were improved in WT mice but not in Arrb2−/− mice. In vivo animal studies for UNC9995 have been conducted in preclinical models of Parkinson's disease and major depressive disorder. The compound prevents neuronal degeneration via a β-arrestin2-biased mechanism. It inhibits NLRP3 inflammasome activation and suppresses JAK/STAT3 pathways. These studies demonstrate the compound’s potential for treating neuroinflammatory conditions. |
| ADME/Pharmacokinetics |
Detailed pharmacokinetic properties of UNC9995 are not extensively reported. The compound has a molecular formula of C20H21Cl2N3OS and a molecular weight of 422.37 g/mol. It is soluble in DMSO at 50 mg/mL (118.38 mM) with ultrasonic warming and heating to 60°C. It appears as a solid powder. Storage: dry, dark, at 0–4°C for short term or -20°C for long term. Purity: 99.9%.
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| Toxicity/Toxicokinetics |
Specific toxicological data for UNC9995 are not detailed in the available literature. The compound is classified for research use only and is not intended for human therapeutic use. As a β-arrestin-2-biased Drd2 agonist that modulates NLRP3 inflammasome activity, potential toxicities would relate to effects on dopaminergic signaling and immune function. Formal toxicological profiles are not reported.
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| References | |
| Additional Infomation |
UNC9995 (CAS 1354030-52-6) is a functionally selective, β-arrestin-2-biased agonist of the dopamine D2 receptor (Drd2). It preferentially activates β-arrestin-2-dependent signaling with an EC50 of 120 nM and Emax of 88%. The compound inhibits NLRP3 inflammasome activation and prevents neuronal degeneration in Parkinson's disease models. No clinical trial or approved indication data are available.
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| Molecular Formula |
C20H21CL2N3OS
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| Molecular Weight |
422.3712413311
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| Exact Mass |
421.078
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| CAS # |
1354030-52-6
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| PubChem CID |
56599143
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| Appearance |
White to off-white solid powder
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| LogP |
5.6
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
27
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| Complexity |
467
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C1CN(CCN1CCCOC2=CC3=C(C=C2)SC=N3)C4=C(C(=CC=C4)Cl)Cl
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| InChi Key |
VBHBKXBUHHJVBZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C20H21Cl2N3OS/c21-16-3-1-4-18(20(16)22)25-10-8-24(9-11-25)7-2-12-26-15-5-6-19-17(13-15)23-14-27-19/h1,3-6,13-14H,2,7-12H2
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| Chemical Name |
5-[3-[4-(2,3-dichlorophenyl)piperazin-1-yl]propoxy]-1,3-benzothiazole
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| HS Tariff Code |
2934.99.9001
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| Storage |
Powder -20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month |
| Shipping Condition |
Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)
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| Solubility (In Vitro) |
DMSO : ~50 mg/mL (~118.38 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.25 mg/mL (2.96 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 12.5 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3676 mL | 11.8380 mL | 23.6759 mL | |
| 5 mM | 0.4735 mL | 2.3676 mL | 4.7352 mL | |
| 10 mM | 0.2368 mL | 1.1838 mL | 2.3676 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.
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