2. GPCR/G Protein Neuronal Signaling
  3. Dopamine Receptor
  4. UNC9995

UNC9995 is a β-arrestin2-biased agonist of dopamine receptor Drd2. UNC9995 inhibits NLRP3 inflammasome activation by enhancing β-arrestin2-NLRP3 interaction, thus prevents neuronal degeneration. Futhermore, UNC9995 activates the Drd2/β-arrestin2 signaling to prevent inflammation-related genes transcription-induced by JAK/STAT3. UNC9995 improves depressive behavior in mouse model, and improves astrocytes dysfunctions.

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UNC9995 Chemical Structure

UNC9995 Chemical Structure

CAS No. : 1354030-52-6

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Based on 1 publication(s) in Google Scholar

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Description

UNC9995 is a β-arrestin2-biased agonist of dopamine receptor Drd2. UNC9995 inhibits NLRP3 inflammasome activation by enhancing β-arrestin2-NLRP3 interaction, thus prevents neuronal degeneration. Futhermore, UNC9995 activates the Drd2/β-arrestin2 signaling to prevent inflammation-related genes transcription-induced by JAK/STAT3. UNC9995 improves depressive behavior in mouse model, and improves astrocytes dysfunctions[1].

IC50 & Target[1]

D2 Receptor

 

In Vitro

UNC9995 (10 μM; 1 h) promotes the combination of STAT3 and β-arrestin2, induced by IL-6 (300 ng/mL; 24 h) in primary astrocytes. And it also inhibits activation of STING, TBK1, JAK[1].
UNC9995 (1, 5, 10, and 20 μM; 1 h) abolishes the apoptosis and inflammation of both WT and Arrb2−/− astrocytes stimulated with IL-6 (300 ng/mL) for 24 h[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

UNC9995 Related Antibodies

Western Blot Analysis[1]

Cell Line: Primary astrocytes
Concentration: 10 μM
Incubation Time: 1 h for pre-incubation; with 300 ng/mL IL-6
Result: Enhanced the interaction between STAT3 and β-arrestin2.
Abolished the activation of cGAS-STING and JAK/STAT3 pathway stimulated by IL-6, decreased the level of p-STING, p-TBK1, p-JAK.
In Vivo

UNC9995 (2 mg/kg/day, i.p, 2 weeks) ameliorates depressive-like behavioral phenotype and improves the loss of astrocytes in the hippocampus in both Chronic social defeated stress (CSDS) model and Chronic unpredictable mild stress (CUMS) model in mouse[1].

MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.

Animal Model: Chronic unpredictable mild stress (CUMS) mouse model[1]
Dosage: 2 mg/kg/d
Administration: IP; 2 weeks
Result: Improved depressive-like symptoms of CUMS mouse model in WT mice but not Arrb2−/− mice.
Molecular Weight

422.37

Formula

C20H21Cl2N3OS
CAS No.
Appearance

Solid

Color

White to off-white

SMILES

ClC1=CC=CC(N2CCN(CC2)CCCOC3=CC4=C(C=C3)SC=N4)=C1Cl
Shipping

Room temperature in continental US; may vary elsewhere.
Storage
Powder -20°C 3 years
4°C 2 years
In solvent -80°C 6 months
-20°C 1 month
Solvent & Solubility
In Vitro: 

DMSO : 50 mg/mL (118.38 mM; ultrasonic and warming and heat to 60°C; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)

Preparing
Stock Solutions
Concentration Solvent Mass 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
View the Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

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Mass (g) = Concentration (mol/L) × Volume (L) × Molecular Weight (g/mol)

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Concentration (start) × Volume (start) = Concentration (final) × Volume (final)

This equation is commonly abbreviated as: C1V1 = C2V2

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In Vivo:

Select the appropriate dissolution method based on your experimental animal and administration route.

For the following dissolution methods, please ensure to first prepare a clear stock solution using an In Vitro approach and then sequentially add co-solvents:
To ensure reliable experimental results, the clarified stock solution can be appropriately stored based on storage conditions. As for the working solution for in vivo experiments, it is recommended to prepare freshly and use it on the same day.
The percentages shown for the solvents indicate their volumetric ratio in the final prepared solution. If precipitation or phase separation occurs during preparation, heat and/or sonication can be used to aid dissolution.

  • Protocol 1

    Add each solvent one by one:  10% DMSO    90% Corn Oil

    Solubility: ≥ 1.25 mg/mL (2.96 mM); Clear solution

    This protocol yields a clear solution of ≥ 1.25 mg/mL (saturation unknown). If the continuous dosing period exceeds half a month, please choose this protocol carefully.

    Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (12.5 mg/mL) to 900 μL Corn oil, and mix evenly.

In Vivo Dissolution Calculator
Please enter the basic information of animal experiments:

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Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
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Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
The co-solvents required include: DMSO, . All of co-solvents are available by MedChemExpress (MCE). , Tween 80. All of co-solvents are available by MedChemExpress (MCE).
Calculation results:
Working solution concentration: mg/mL
Method for preparing stock solution: mg drug dissolved in μL  DMSO (Stock solution concentration: mg/mL).
The concentration of the stock solution you require exceeds the measured solubility. The following solution is for reference only. If necessary, please contact MedChemExpress (MCE).
Method for preparing in vivo working solution for animal experiments: Take μL DMSO stock solution, add μL . μL , mix evenly, next add μL Tween 80, mix evenly, then add μL Saline.
 If the continuous dosing period exceeds half a month, please choose this protocol carefully.
Please ensure that the stock solution in the first step is dissolved to a clear state, and add co-solvents in sequence. You can use ultrasonic heating (ultrasonic cleaner, recommended frequency 20-40 kHz), vortexing, etc. to assist dissolution.
Purity & Documentation
References

Complete Stock Solution Preparation Table

* Please refer to the solubility information to select the appropriate solvent. Once prepared, please aliquot and store the solution to prevent product inactivation from repeated freeze-thaw cycles.
Storage method and period of stock solution: -80°C, 6 months; -20°C, 1 month. When stored at -80°C, please use it within 6 months. When stored at -20°C, please use it within 1 month.

Optional Solvent Concentration Solvent Mass 1 mg 5 mg 10 mg 25 mg
DMSO 1 mM 2.3676 mL 11.8380 mL 23.6759 mL 59.1898 mL
5 mM 0.4735 mL 2.3676 mL 4.7352 mL 11.8380 mL
10 mM 0.2368 mL 1.1838 mL 2.3676 mL 5.9190 mL
15 mM 0.1578 mL 0.7892 mL 1.5784 mL 3.9460 mL
20 mM 0.1184 mL 0.5919 mL 1.1838 mL 2.9595 mL
25 mM 0.0947 mL 0.4735 mL 0.9470 mL 2.3676 mL
30 mM 0.0789 mL 0.3946 mL 0.7892 mL 1.9730 mL
40 mM 0.0592 mL 0.2959 mL 0.5919 mL 1.4797 mL
50 mM 0.0474 mL 0.2368 mL 0.4735 mL 1.1838 mL
60 mM 0.0395 mL 0.1973 mL 0.3946 mL 0.9865 mL
80 mM 0.0296 mL 0.1480 mL 0.2959 mL 0.7399 mL
100 mM 0.0237 mL 0.1184 mL 0.2368 mL 0.5919 mL
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UNC9995 Related Classifications

Help & FAQs
  • Do most proteins show cross-species activity?

    Species cross-reactivity must be investigated individually for each product. Many human cytokines will produce a nice response in mouse cell lines, and many mouse proteins will show activity on human cells. Other proteins may have a lower specific activity when used in the opposite species.

Keywords:

UNC99951354030-52-6UNC 9995UNC-9995Dopamine ReceptorInhibitorinhibitorinhibit

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