| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Human CXCR3
CXCR3 (CXC chemokine receptor 3). PS372424 hydrochloride is a specific human CXCR3 agonist that binds to the receptor with a binding affinity of 42 nM. It acts as a peptidomimetic mimic of the natural ligand CXCL10 (IP-10), activating CXCR3 signaling and modulating T-cell chemotaxis. |
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| ln Vitro |
In U87-CXCR3-A cells, PS372424 (100 ng/mL) raises p-Erk1 and p-Erk2 after 5 minutes of stimulation[1]. CCR5 on CXCR3+ T cells, but not on CXCR3- T cells, is phosphorylated in response to concentration when exposed to PS372424 (10-200 nM; 30 min)[2]. At an IC50 of 42±21 nM, PS372424 competes with radiolabeled CXCL10 for binding to membranes made from HEK293/CXCR3 Gqi5 cells[3].
In vitro, PS372424 hydrochloride is a potent, selective peptidomimetic agonist of human CXCR3, with an EC50 of 1.1 uM in calcium flux assays and a binding affinity (Kd) of 42 nM. As a three-amino-acid fragment of CXCL10, it activates CXCR3-mediated signaling pathways, including calcium mobilization and intracellular signaling events. It also has anti-inflammatory activity in cell-based models. |
| ln Vivo |
In vivo, PS372424 hydrochloride prevents human T-cell migration in a humanized model of arthritic inflammation. By activating CXCR3, it modulates chemotaxis and reduces the accumulation of T cells in inflamed joints. This anti-inflammatory effect suggests potential for studying CXCR3 as a therapeutic target in rheumatoid arthritis and other Th1-mediated autoimmune diseases.
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| Enzyme Assay |
A radioligand binding assay is used to determine CXCR3 binding affinity. Membranes from CXCR3-expressing cells are incubated with a radiolabeled CXCR3 ligand in the presence of serially diluted PS372424 hydrochloride (0.1-1000 nM). Bound radioactivity is measured by filtration and scintillation counting, and the Kd is calculated. For functional activation, a calcium flux assay is performed using CXCR3-expressing cells loaded with a calcium-sensitive dye (e.g., Fluo-4).
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| Cell Assay |
Western Blot Analysis[2]
Cell Types: CXCR3+ T cells and CXCR3- T cells Tested Concentrations: 10, 50, 100, or 200 nM Incubation Duration: 30 minutes Experimental Results: Caused a concentration-dependent phosphorylation of CCR5 on CXCR3+ T cells. Did not result in phosphorylation of CCR5 on CXCR3- T cells. For in vitro chemotaxis assays, human peripheral blood T cells are isolated from healthy donors by magnetic bead separation (CD4+ or CD8+). T cells are labeled with a fluorescent dye and placed in the upper chamber of a transwell plate (5 um pore size). The lower chamber contains a CXCR3 agonist (e.g., CXCL10 or PS372424 hydrochloride) at specified concentrations, with or without PS372424 hydrochloride. After 2-4 hours, migrated cells are quantified by fluorescence spectrophotometry. CXCR3 signaling is assessed by measuring calcium flux or ERK phosphorylation by Western blot. |
| Animal Protocol |
In a humanized mouse model of arthritic inflammation, immunodeficient NSG mice are engrafted with human PBMCs to reconstitute a human immune system. Arthritis is induced by injection of anti-type II collagen antibodies or by transfer of human T cells. PS372424 hydrochloride is administered intraperitoneally or intravenously at doses of 1-20 mg/kg daily or every other day for 2-4 weeks. Paw swelling is measured, and clinical arthritis scores are assessed. Joint tissues are harvested for histopathological analysis (H&E and safranin O staining). Human T-cell infiltration into joints is assessed by immunohistochemistry (IHC) for human CD3, CD4, or CD8.
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| ADME/Pharmacokinetics |
PS372424 hydrochloride has a molecular weight of approximately 400-500 g/mol (peptidomimetic). Detailed PK parameters are not publicly available. As a small peptide-like compound, it is expected to have moderate stability in plasma and may be susceptible to proteolytic degradation. It is typically administered intraperitoneally or intravenously in research settings, with oral bioavailability likely low. It is supplied as a hydrochloride salt for improved solubility.
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| Toxicity/Toxicokinetics |
Detailed toxicological data for PS372424 hydrochloride are not publicly available. Based on its mechanism as a CXCR3 agonist, potential adverse effects may include modulation of T-cell trafficking and immune function, though no significant toxicities have been reported at therapeutic doses in research models. In cell-based assays, no cytotoxicity has been observed at concentrations up to 100 uM. Long-term safety studies have not been conducted.
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| References |
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| Additional Infomation |
PS372424 hydrochloride is a research-grade compound not approved for clinical use. It is a peptidomimetic CXCR3 agonist derived from CXCL10, used to study the role of CXCR3 in T-cell migration, inflammation, and autoimmune diseases such as rheumatoid arthritis and multiple sclerosis. This product is for laboratory research purposes only, not for human therapeutic use.
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| Molecular Formula |
C33H45CLN6O4
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|---|---|
| Molecular Weight |
625.201206922531
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| Exact Mass |
624.319
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| CAS # |
1596362-29-6
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| Related CAS # |
PS372424;914291-61-5
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| PubChem CID |
117064650
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
5
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
44
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| Complexity |
970
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| Defined Atom Stereocenter Count |
2
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| SMILES |
Cl.O=C([C@H](CCC/N=C(\N)/N)NC([C@@H]1CC2C=CC=CC=2CN1C(CCC(C1C=CC=CC=1)=O)=O)=O)NCC1CCCCC1
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| InChi Key |
XHGSJQNAEULTAR-DHBRAOIWSA-N
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| InChi Code |
InChI=1S/C33H44N6O4.ClH/c34-33(35)36-19-9-16-27(31(42)37-21-23-10-3-1-4-11-23)38-32(43)28-20-25-14-7-8-15-26(25)22-39(28)30(41)18-17-29(40)24-12-5-2-6-13-24;/h2,5-8,12-15,23,27-28H,1,3-4,9-11,16-22H2,(H,37,42)(H,38,43)(H4,34,35,36);1H/t27-,28-;/m0./s1
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| Chemical Name |
(3S)-N-[(2S)-1-(cyclohexylmethylamino)-5-(diaminomethylideneamino)-1-oxopentan-2-yl]-2-(4-oxo-4-phenylbutanoyl)-3,4-dihydro-1H-isoquinoline-3-carboxamide;hydrochloride
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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 Note: Please store this product in a sealed and protected environment, avoid exposure to moisture. |
| 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: 250 mg/mL (399.87 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (3.33 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 (3.33 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 (3.33 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 | 1.5995 mL | 7.9974 mL | 15.9949 mL | |
| 5 mM | 0.3199 mL | 1.5995 mL | 3.1990 mL | |
| 10 mM | 0.1599 mL | 0.7997 mL | 1.5995 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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