| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| 5mg | |||
| Other Sizes |
| Targets |
Retinoid X receptors (RXRα, RXRβ, and RXRγ). IRX4204 shows high affinity for all three RXR subtypes with Kd values of 0.4 nM for RXRα, 3.6 nM for RXRβ, and 3.8 nM for RXRγ. It has no activity on RAR.
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| ln Vitro |
In RAW264.7 macrophages, treatment with AGN194204 (NRX194204; 0-100 nM; 24 hours; E) inhibits the release of nitric oxide and interleukin-6, as well as the degradation of IKBα, caused by lipopolysaccharide and tumor necrosis factor-α. Similar to cells, capacities [1]. Breast cancer cells undergo apoptosis when treated with AGN194204 (NRX194204; 1 μM; 72 hours; SK-BR-3 human breast cancer cells) [1].
IRX4204 binds to RXRα, RXRβ, and RXRγ with Kd values of 0.4 nM, 3.6 nM, and 3.8 nM, respectively. EC50 values are 0.2 nM for RXRα, 0.8 nM for RXRβ, and 0.08 nM for RXRγ. The compound shows no activity on retinoic acid receptors (RAR). These values demonstrate high potency and RXR selectivity. |
| ln Vivo |
The number and size of lung surface tumors as well as the total tumor volume per slide were considerably reduced by AGN194204 (NRX194204; 30–60 mg/kg; oral; daily; for 15 weeks; female A/J mice) treatment. The reduction was 64%–81% when compared to the control group [1].
In vivo, IRX4204 has been evaluated in clinical trials for Parkinson's disease (NCT02438215) and non-small cell lung cancer. As an orally bioavailable RXR agonist, it shows potential antitumor and anti-inflammatory activities. Specific preclinical in vivo efficacy data including animal model results are limited in publicly available literature. |
| Enzyme Assay |
RXR binding affinity is assessed using in vitro radioligand binding assays with recombinant RXRα, RXRβ, and RXRγ proteins. Competitive binding with [3H]9-cis-retinoic acid is measured. RXR agonist activity is evaluated using reporter gene assays in cells transfected with RXR and a luciferase reporter. EC50 values are calculated from dose-response curves.
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| Cell Assay |
Apoptosis analysis[1]
Cell Types: SK-BR-3 human breast cancer cells Tested Concentrations: 1 μM Incubation Duration: 72 hrs (hours) Experimental Results: Induction of apoptosis in lung and breast cancer cells. Western Blot Analysis[1] Cell Types: E, RAW Cell Tested Concentrations: 0 nM, 1 nM, 10 nM and 100 nM Incubation Duration: 24 hrs (hours) Experimental Results: Ability to block the release of nitric acid induced by lipopolysaccharide and tumor necrosis factor-alpha oxides and interleukin-6 and degradation of IKBα in RAW264.7 macrophage-like cells. Cellular activity is evaluated in RXR-responsive reporter gene assays. Cells are transfected with RXR expression constructs and luciferase reporter plasmids, treated with IRX4204 at various concentrations, and luciferase activity is measured. RAR activity is assessed in parallel to confirm selectivity. Antiproliferative effects are evaluated in cancer cell lines. |
| Animal Protocol |
Animal/Disease Models: Female A/J mice vinyl carbamate [1]
Doses: 30 mg/kg, 60 mg/kg Route of Administration: oral; daily; for 15 weeks Experimental Results: Compared with the control group, lung surface The number and size of tumors was Dramatically diminished, with the total tumor volume per slide diminished by 64% to 81%. In vivo efficacy is evaluated in clinical trials for Parkinson's disease and non-small cell lung cancer. Preclinical animal studies are conducted in mouse xenograft models of cancer or models of neurodegeneration. IRX4204 is administered orally at various doses, and tumor growth, survival, or neurological function is assessed. |
| ADME/Pharmacokinetics |
IRX4204 is orally bioavailable with a molecular formula of C24H32O2. The compound should be stored as powder at -20°C for up to 3 years or in solvent at -80°C for 6 months. Detailed pharmacokinetic parameters including half-life, Cmax, and AUC are available from clinical studies but not detailed in public search results.
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| Toxicity/Toxicokinetics |
Safety data from clinical trials indicate IRX4204 is generally well-tolerated. As a retinoid X receptor agonist, potential side effects may include those associated with retinoid类药物 such as skin dryness, lipid profile changes, and teratogenicity. The compound should not be used in pregnancy. Full toxicological profiles are available from clinical study reports.
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| References |
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| Additional Infomation |
Nrx194204 has been used in investigational clinical trials for the treatment of Parkinson's disease and non-small cell lung cancer. Rexinoid NRX 194204 is an orally bioavailable synthetic retinoid X receptor (RXR) agonist with potential antitumor and anti-inflammatory activities. Rexinoid NRX 194204 selectively binds to and activates RXR. Because RXR can form heterodimers with various nuclear receptors (NR), activation of RXR by this drug may lead to broad gene expression, depending on the effector DNA response elements activated. Rexinoid NRX 194204 inhibits tumor necrosis factor (TNF)-mediated release of nitric oxide (NO) and interleukin-6 (IL-6) and may inhibit tumor cell proliferation. The drug appears to have lower toxicity than RAR-selective ligands.
IRX4204 has been investigated in clinical trials for Parkinson's disease (NCT02438215) and non-small cell lung cancer. It is an orally bioavailable synthetic RXR agonist with potential antineoplastic and anti-inflammatory activities. The compound is not yet approved for clinical use but has shown promise in early-phase trials. It is also known as NRX-194204 and AGN-194204. |
| Molecular Formula |
C24H32O2
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|---|---|
| Molecular Weight |
352.51
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| Exact Mass |
352.24
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| CAS # |
220619-73-8
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| PubChem CID |
9863341
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| Appearance |
White to off-white solid powder
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| LogP |
5.9
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
4
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| Heavy Atom Count |
26
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| Complexity |
624
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| Defined Atom Stereocenter Count |
2
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| SMILES |
C/C(=C\C(=O)O)/C=C/[C@@H]1C[C@]1(C)C2=CC3=C(C=C2)C(CCC3(C)C)(C)C
|
| InChi Key |
BOOOLEGQBVUTKC-NVQSDHBMSA-N
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| InChi Code |
InChI=1S/C24H32O2/c1-16(13-21(25)26)7-8-18-15-24(18,6)17-9-10-19-20(14-17)23(4,5)12-11-22(19,2)3/h7-10,13-14,18H,11-12,15H2,1-6H3,(H,25,26)/b8-7+,16-13+/t18-,24-/m1/s1
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| Chemical Name |
(2E,4E)-3-methyl-5-[(1S,2S)-2-methyl-2-(5,5,8,8-tetramethyl-6,7-dihydronaphthalen-2-yl)cyclopropyl]penta-2,4-dienoic acid
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| Synonyms |
IRX 4204; IRX-4204; IRX4204
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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 : ~35 mg/mL (~99.29 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 | 2.8368 mL | 14.1840 mL | 28.3680 mL | |
| 5 mM | 0.5674 mL | 2.8368 mL | 5.6736 mL | |
| 10 mM | 0.2837 mL | 1.4184 mL | 2.8368 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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