| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Targets |
Human CXCR3
PS372424 HCl specifically targets the human CXC chemokine receptor 3 (CXCR3). It is a potent agonist of this receptor, with an IC50 of 42 nM for preventing the binding of the natural CXCR3 ligand, CXCL10. The compound functions by mimicking the CXCL10 fragment, thereby binding to the CXCR3 receptor and triggering downstream signaling pathways. This interaction is key to its anti-inflammatory activity, as it can influence T cell migration and activation. |
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| ln Vitro |
PS372424 (100 ng/mL) increases p-Erk1 and p-Erk2 after 5 minutes of stimulation in U87-CXCR3-A cells[1].
PS372424 (10-200 nM; 30 min) phosphorylates CCR5 in a concentration-dependent manner on CXCR3+ T cells not in CXCR3- T cells[2]. PS372424 competes for the binding of radiolabeled CXCL10 to membranes prepared from HEK293/CXCR3 Gqi5 cells with an IC50 of 42±21 nM[3]. In vitro, PS372424 HCl demonstrates potent agonistic activity at CXCR3. It competes for the binding of radiolabeled CXCL10 to membranes prepared from HEK293/CXCR3 Gqi5 cells with an IC50 of 42 nM. In cell-based assays, treatment with PS372424 HCl (100 ng/mL) increases the phosphorylation of ERK1 and ERK2 after 5 minutes of stimulation in U87-CXCR3-A cells. Furthermore, it causes a concentration-dependent phosphorylation of CCR5 on CXCR3+ T cells but not on CXCR3- T cells, demonstrating its receptor-specific activity. |
| ln Vivo |
The in vivo activity of PS372424 HCl has been demonstrated in animal models. It has been shown to block CXCL11-induced migration of CD45+ cells to air pouches generated on humanized mice. In arthritis inflammation models, PS372424 inhibits T cell migration, confirming its anti-inflammatory potential. These studies indicate that the compound is effective in modulating immune cell trafficking in a living organism, supporting its potential therapeutic application in inflammatory diseases.
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| Enzyme Assay |
Cell-free receptor binding assays are used to characterize the affinity of PS372424 HCl for CXCR3. A common method is a radioligand binding assay. Membranes are prepared from cells that overexpress the human CXCR3 receptor. These membranes are then incubated with a fixed concentration of a radiolabeled CXCR3 ligand (e.g., [125I]-CXCL10) and varying concentrations of PS372424 HCl. After incubation, the mixture is filtered to separate bound from free radioligand, and the radioactivity on the filters is measured. The concentration of PS372424 HCl that inhibits 50% of the radioligand binding (IC50) is then calculated.
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| Cell Assay |
Cell Line: CXCR3+ T cells and CXCR3- T cells
Concentration: 10, 50, 100, or 200 nM Incubation Time: 30 minutes Result: Caused a concentration-dependent phosphorylation of CCR5 on CXCR3+ T cells. Did not result in phosphorylation of CCR5 on CXCR3- T cells. In vitro cell-based assays for PS372424 HCl are performed to study its signaling and functional effects. To evaluate receptor activation, cells expressing CXCR3 (e.g., U87-CXCR3-A cells) are treated with the compound. The activation of downstream signaling pathways is then assessed. For example, cells can be lysed, and the phosphorylation of ERK1/2 is detected via Western blotting using phospho-specific antibodies. To study its effect on cell migration, chemotaxis assays are used. CXCR3+ T cells are placed in the upper chamber of a transwell plate, and PS372424 HCl or a CXCR3 ligand is added to the lower chamber. The number of cells that migrate to the lower chamber is then counted. |
| Animal Protocol |
In vivo animal experiments for PS372424 HCl involve models of inflammation. One described model is the air pouch model in humanized mice. In this model, an air pouch is created on the back of the mouse, and an inflammatory stimulus is injected into the pouch. PS372424 HCl is then administered, and its effect on the migration of immune cells (e.g., CD45+ cells) into the pouch is measured. In arthritis models, the compound is administered to arthritic mice, and the reduction in T cell migration and the associated inflammatory response are assessed as measures of efficacy.
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| ADME/Pharmacokinetics |
Pharmacokinetic (PK) data for PS372424 HCl is not extensively detailed in the public literature. As a peptidomimetic compound, its properties, such as bioavailability and half-life, would be key factors in its development. Given that it has shown in vivo activity, it is likely to have sufficient stability and exposure in the body. However, detailed PK parameters like Cmax, Tmax, AUC, and protein binding are not reported in the available sources. The compound is typically stored as a powder at -20°C.
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| Toxicity/Toxicokinetics |
Toxicological data for PS372424 HCl is limited. As a research compound, its safety profile is not extensively documented in the public domain. However, its mechanism of action, involving modulation of the immune system, suggests that potential toxicities could be related to immune dysfunction. The specific LD50, organ toxicity, and genotoxicity are not available. Its use is strictly for research purposes and not for human therapeutic use.
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| References |
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| Additional Infomation |
PS372424 HCl is a research-grade compound used to study the role of the CXCR3 chemokine receptor in various biological processes, particularly in inflammation and immune cell trafficking. It is a valuable tool for probing the function of CXCR3 in T cell biology and for validating the receptor as a potential therapeutic target for autoimmune and inflammatory diseases. It has not been approved for clinical use. All information is for research reference and not for diagnostic or clinical use.
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| Molecular Formula |
C33H45CLN6O4
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|---|---|
| Molecular Weight |
625.201206922531
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| Exact Mass |
624.32
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| CAS # |
914291-61-5
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| Related CAS # |
PS372424 hydrochloride; 1596362-29-6
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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)
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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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| Synonyms |
PS 372424 HCl; PS-372424 HCl; PS372424 HCl; PS372424 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 |
| 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 (~399.9 mM)
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| Solubility (In Vivo) |
Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples.
Injection Formulations
Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline)(e.g. IP/IV/IM/SC) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). View More
Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] Oral Formulations
Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). View More
Oral Formulation 3: Dissolved in PEG400 (Please use freshly prepared in vivo formulations for optimal results.) |
| 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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