HEP-50768
HEP-50768 is an orally active and selective MRGPRX4 (hX4) antagonist. HEP-50768 suppresses basal and bile-acid-stimulated hX4 activity. HEP-50768 binds the receptor’s transmembrane pocket and induces extracellular loop rearrangements. HEP-50768 modulates GPCR microswitch motifs and reduces bile-acid-induced pruritic scratching behaviors. HEP-50768 can be used for the research of cholestatic pruritus.
For research use only. We do not sell to patients.
- CAS No.: 3036387-75-1
- Formula: C16H10F4N4O
- Molecular Weight:350.27
-
Storage:
Please store the product under the recommended conditions in the Certificate of Analysis.
-
Biological Activity
-
Chemical Information
-
Solvent & Solubility
- Purity & Documentation
- References
-
Help & FAQs
Biological Activity
HEP-50768 (1 nM-1 μM; 30 min) potently inhibits DCA-induced calcium mobilization in HEK293T cells stably expressing hX4 with an IC50 of 14 nM and achieves 100% inhibition at 2 μM[1].
HEP-50768 (0.1 μM) acts as an inverse agonist, significantly reducing basal inositol monophosphate levels in HEK293T cells expressing hX4[1].
HEP-50768 (2 μM; 1.5 h) modestly reduces GTPase activity of the purified hX4-Gq complex, consistent with its inverse agonist activity[1].
HEP-50768 (0.02-50 nM) binds purified apo hX4 and hX4-miniGαq complex with high, comparable affinity, exhibiting K0 values of 0.6 nM and 0.7 nM, respectively[1].
HEP-50768 (0.1 nM-10 mM; 30 min) is highly selective for hX4, showing weak inhibition of hX1 (IC50 = 16 μM) and hX2 (IC50 = 1.5 μM) with no agonist activity against either receptor[1].
HEP-50768 (~5 min) shows minimal hERG channel inhibition in HEK293 cells stably expressing hERG, with an IC50 exceeding 30 μM[1].
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
MedChemExpress (MCE) has not independently confirmed the accuracy of these methods. They are for reference only.
-
Animal Model:hX4-humanized rats (generated by crossing MRGA::hX4-Cre rats with Rosa26::lsl-hX4 rats)[1]
-
Dosage:5 mg/kg; 10 mg/kg
-
Administration:p.o.; single dose; 2.5 hours before pruritus induction
-
Result:Significantly reduced DCA-3S-induced scratching bouts compared to PBS vehicle control with a P-value of 0.0059 (5 mg/kg dose).
Significantly reduced DCA-3S-induced scratching bouts compared to PBS vehicle control with a P-value of 0.0049 (10 mg/kg dose).
Chemical Information
-
CAS No. 3036387-75-1
-
Molecular Weight 350.27
-
Formula C16H10F4N4O
-
SMILES
FC1=C(C2=NN=NN2)C=CC=C1[C@@H]3CC4=CC(C(F)(F)F)=CC=C4O3
-
Shipping
Room temperature in continental US; may vary elsewhere.
-
Storage
Please store the product under the recommended conditions in the Certificate of Analysis.
Solvent & Solubility
DMSO : 100 mg/mL (285.49 mM; Need ultrasonic; Hygroscopic DMSO has a significant impact on the solubility of product, please use newly opened DMSO)
Concentration (start) × Volume (start) = Concentration (final) × Volume (final)
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.
Add each solvent one by one: 10% DMSO 40% PEG300 5% Tween-80 45% Saline
Solubility: ≥ 2.5 mg/mL (7.14 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 400 μL PEG300, and mix evenly; then add 50 μL Tween-80 and mix evenly; then add 450 μL Saline to adjust the volume to 1 mL.
Preparation of Saline: Dissolve 0.9 g sodium chloride in ddH₂O and dilute to 100 mL to obtain a clear Saline solution.
Add each solvent one by one: 10% DMSO 90% (20% SBE-β-CD in Saline)
Solubility: ≥ 2.5 mg/mL (7.14 mM); Clear solution
This protocol yields a clear solution of ≥ 2.5 mg/mL (saturation unknown).
Taking 1 mL working solution as an example, add 100 μL DMSO stock solution (25.0 mg/mL) to 900 μL 20% SBE-β-CD in Saline, and mix evenly.
Preparation of 20% SBE-β-CD in Saline (4°C, storage for one week): 2 g SBE-β-CD powder is dissolved in 10 mL Saline, completely dissolve until clear.
Please enter the basic information of animal experiments:
-
-
-
-
Recommended: Prepare an additional quantity of animals to account for potential losses during experiments.
Please enter your animal formula composition:
-
%DMSO +
Recommended: Keep the proportion of DMSO in working solution below 2% if your animal is weak.
-
%+
-
+%Tween-80 + +
-
%Saline +
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).
Working solution concentration: 0.22 mg/mL
Method for preparing stock solution: mg drug dissolved in μL DMSO. Stock solution concentration: mg/mL.
1. Take μL DMSO stock solution;
2. Add μL .
μL , mix evenly;
3. Then add μL Tween 80, mix evenly;
4. Then add μL
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
| Optional Solvent | Concentration Solvent Mass | 1 mg | 5 mg | 10 mg | 25 mg |
|---|---|---|---|---|---|
| DMSO | 1 mM | 2.8549 mL | 14.2747 mL | 28.5494 mL | 71.3735 mL |
| 5 mM | 0.5710 mL | 2.8549 mL | 5.7099 mL | 14.2747 mL | |
| 10 mM | 0.2855 mL | 1.4275 mL | 2.8549 mL | 7.1374 mL | |
| 15 mM | 0.1903 mL | 0.9516 mL | 1.9033 mL | 4.7582 mL | |
| 20 mM | 0.1427 mL | 0.7137 mL | 1.4275 mL | 3.5687 mL | |
| 25 mM | 0.1142 mL | 0.5710 mL | 1.1420 mL | 2.8549 mL | |
| 30 mM | 0.0952 mL | 0.4758 mL | 0.9516 mL | 2.3791 mL | |
| 40 mM | 0.0714 mL | 0.3569 mL | 0.7137 mL | 1.7843 mL | |
| 50 mM | 0.0571 mL | 0.2855 mL | 0.5710 mL | 1.4275 mL | |
| 60 mM | 0.0476 mL | 0.2379 mL | 0.4758 mL | 1.1896 mL | |
| 80 mM | 0.0357 mL | 0.1784 mL | 0.3569 mL | 0.8922 mL | |
| 100 mM | 0.0285 mL | 0.1427 mL | 0.2855 mL | 0.7137 mL |
Powered by Bioz