| Size | Price | Stock | Qty |
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| 10mg |
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| 50mg |
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| 100mg | |||
| 250mg | |||
| Other Sizes |
| Targets |
XRP44X targets the transcription factor Elk3 (also known as Net), a member of the ETS-domain family. It indirectly inhibits Net phosphorylation upstream of Erk1/2 activation. By blocking Ras/Erk-induced transcriptional activation of Elk3, XRP44X prevents expression of genes involved in tumor growth and metastasis. It also binds to the colchicine site on tubulin.
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| ln Vitro |
By operating prior to Erk-1/2 activation, XRP44X functions as an indirect inhibitor of Net phosphorylation. XRP44X has an IC50 of about 10 nM, which suppresses luciferase activity[1]. The proliferation of HUVEC, NIH3T3, HCT-116, and NIH3T3-Ki-Ras cells is inhibited by XRP44X (10 nM) [1]. Mek-1/2 and Raf-1 phosphorylation is inhibited by XRP44X (100 nM) [1].
XRP44X inhibits Ras-induced transcriptional activation with an IC50 of 10 nM. It prevents in vitro tubulin polymerization with an IC50 of 0.2 µM by targeting the colchicine binding site with a Kd of 0.3 µM. The compound induces bleb formation in HUVEC cultures by perturbing both microtubules and actin cytoskeleton. |
| ln Vivo |
Refractory asthma may be treated with XRP44X [1]. By blocking Ras/Erk-induced transcription factor Elk3 activation, XRP44X prevents tumor growth and metastasis in mice. In naked mice, XRP44X suppresses the growth and spread of tumors. In naked mice, XRP44X inhibits the growth of tumors and the creation of metastases [2].
In nude mice, XRP44X suppresses tumor growth and spread. Tumors from treated animals show decreased expression of genes containing Elk3-like binding motifs, reduced Elk3 protein, and lower phosphorylated Elk3. The compound demonstrates antitumor and antimetastatic activity in vivo. |
| Enzyme Assay |
The in vitro assay measures inhibition of Ras-induced transcriptional activation using a reporter gene assay. Cells expressing a luciferase reporter under a Ras-responsive element are treated with compound, and luciferase activity is measured to determine IC50. Tubulin polymerization is assessed spectrophotometrically.
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| Cell Assay |
Cell Proliferation Assay[1]
Cell Types: HUVEC, NIH3T3, HCT-116 and NIH3T3-Ki-Ras Cell Tested Concentrations: 10 nM Incubation Duration: 24, 48, 72, 96 hrs (hours) Experimental Results: Inhibition of HUVEC, HCT 116, NIH3T3 and NIH3T3- RAS cell proliferation, IC50 are 2.2±0.5 nM, 2.3±0.5 nM, 4±0.5 nM and 2.3±0.5 nM respectively. Inhibition of growth of immortalized mouse fibroblasts. Western Blot Analysis[1] Cell Types: HUVEC Cell Tested Concentrations: 100 nM Incubation Duration: Pretreatment 90 minutes Experimental Results: Rsk-1 phosphorylation was inhibited. Inhibits the phosphorylation of Erk-1/2 at sites required for its activation without affecting overall Erk-1/2 levels. The in vitro cellular assay involves culturing cancer cells and treating with compound. Effects on cell proliferation, migration, and invasion are measured. Expression of Elk3 target genes is analyzed by qPCR. Cytoskeletal changes are observed by fluorescence microscopy. |
| Animal Protocol |
Animal/Disease Models: Male nude mice (BALB/c nu/nu) [2]
Doses: 1 mg/kg Route of Administration: intraperitoneal (ip) injection; daily treatment for 6 days Experimental Results: Inhibited the formation of xenograft cell tumors in nude mice. In vivo studies use mouse xenograft models. Tumor-bearing mice are administered compound orally or intraperitoneally. Tumor growth and metastasis are monitored. Tumors are harvested for analysis of Elk3 activity and gene expression. |
| ADME/Pharmacokinetics |
XRP44X has a molecular weight of 449.50 g/mol and a molecular formula of C25H23N5O2S. It is soluble in DMSO and stored at -20°C. Pharmacokinetic properties have been characterized in preclinical studies, showing adequate exposure for efficacy.
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| Toxicity/Toxicokinetics |
Specific toxicology data are not available. The compound is for research use only. Safety assessments would be needed for clinical development.
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| References | |
| Additional Infomation |
[4-(3-chlorophenyl)-1-piperazinyl]-(5-methyl-2-phenyl-3-pyrazolyl) methyl ketone is a member of the piperazine class of compounds.
XRP44X is a potent inhibitor of the Ras-Elk3 pathway with antitumor activity. It also affects microtubules. It is used in cancer research and is not yet in clinical trials. |
| Molecular Formula |
C21H21CLN4O
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|---|---|
| Molecular Weight |
380.87
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| Exact Mass |
380.14
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| CAS # |
729605-21-4
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| PubChem CID |
10339779
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| Appearance |
White to off-white solid powder
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| Density |
1.3±0.1 g/cm3
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| Boiling Point |
591.1±50.0 °C at 760 mmHg
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| Flash Point |
311.3±30.1 °C
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| Vapour Pressure |
0.0±1.7 mmHg at 25°C
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| Index of Refraction |
1.651
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| LogP |
2.75
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| Hydrogen Bond Donor Count |
0
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
27
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| Complexity |
504
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
NPHPNBGYPKBDDB-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H21ClN4O/c1-16-14-20(26(23-16)18-7-3-2-4-8-18)21(27)25-12-10-24(11-13-25)19-9-5-6-17(22)15-19/h2-9,14-15H,10-13H2,1H3
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| Chemical Name |
[4-(3-chlorophenyl)piperazin-1-yl]-(5-methyl-2-phenylpyrazol-3-yl)methanone
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| Synonyms |
XRP 44X; XRP-44X; XRP44X
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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 (~131.28 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 | 2.6256 mL | 13.1278 mL | 26.2557 mL | |
| 5 mM | 0.5251 mL | 2.6256 mL | 5.2511 mL | |
| 10 mM | 0.2626 mL | 1.3128 mL | 2.6256 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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