| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| 25mg | |||
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| Other Sizes |
| Targets |
IRX5183 targets retinoic acid receptor alpha (RARα), a nuclear receptor that regulates gene transcription. Upon binding, it activates RARα-mediated signaling, which promotes the transcription of RARα-responsive genes responsible for cellular differentiation and proliferation. It has no activity on RARβ/γ, demonstrating its high selectivity.
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| ln Vitro |
AGN-195183 (IRX-5183; Compound 4) suppresses the development of breast cancer cell lines and is inert in an in vivo model of local stimulation. AGN-195183 and ATRA limit the proliferation of human breast cancer cell lines T-47D and SK-BR-3. AGN-195183 does not produce local irritation caused by RARa-selective retinol Am-580. AGN-195183 is now in Phase I/IIA clinical trials in cancer patients.
In vitro, IRX5183 binds to and activates RARα. Its binding Kd of 3 nM indicates very high affinity for its target. Its improved binding selectivity relative to other RAR agonists makes it a valuable tool for studying RARα-specific signaling pathways. |
| ln Vivo |
In vivo, IRX5183 significantly reduces albuminuria and normalizes blood pressure in nephritic rats. It lowers the glomerulosclerosis index, glomerular cell and interstitial cell counts, and the area of the interstitial space. These effects demonstrate its potential for treating renal diseases.
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| Enzyme Assay |
RARα binding affinity is determined using radioligand binding assays. Membrane preparations or purified RARα protein are incubated with varying concentrations of IRX5183 and a radiolabeled ligand. The Kd value is calculated from binding curves.
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| Cell Assay |
Functional activity is assessed in cells expressing RARα. The compound's ability to activate RARα-mediated transcription is measured using reporter gene assays. A dose-response curve is generated, and the EC50 is calculated.
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| Animal Protocol |
In vivo efficacy is evaluated in animal models of renal disease, such as nephritic rats. IRX5183 is administered orally, and markers of renal function, such as albuminuria and blood pressure, are measured. Histopathological analysis of kidney tissue is also performed.
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| ADME/Pharmacokinetics |
IRX5183 is orally bioavailable. Its pharmacokinetic properties are consistent with a small molecule RAR agonist. Its selectivity for RARα may contribute to a favorable pharmacokinetic and toxicity profile.
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| Toxicity/Toxicokinetics |
As a RARα agonist, potential toxicities may include those associated with retinoid therapy, such as skin dryness, mucous membrane irritation, and teratogenicity. Its selectivity for RARα over other RAR subtypes may reduce some of these effects.
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| References | |
| Additional Infomation |
RARα agonist IRX5183 is an orally bioavailable retinoic acid receptor α (RARα) agonist and vitamin A derivative with potential antitumor activity. Upon administration, IRX5183 binds to and activates RARα, thereby promoting RARα-mediated signaling. This leads to the transcription of RARα-responsive genes responsible for cell differentiation and proliferation. Ultimately, this results in the induction of cell differentiation and apoptosis, and the inhibition of cell proliferation and tumorigenesis. RARα is a nuclear receptor belonging to the steroid receptor superfamily. Attenuated RARα signaling is associated with cancer development in various cancer cell types.
Drug Indications It has been investigated for the treatment of adverse reactions to chemotherapy and hematological disorders (hematopoietic organ diseases, not specified). Mechanism of Action VTP-195183 is a retinoic acid receptor α (RARα) specific agonist. IRX5183 is a research compound that has been studied for its potential in treating renal diseases and cancer. Its potent and selective activation of RARα makes it a valuable tool for studying RARα-mediated signaling pathways and for developing new therapies for diseases involving RARα dysregulation. |
| Molecular Formula |
C22H22CLF2NO4
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|---|---|
| Molecular Weight |
437.8642
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| Exact Mass |
437.12
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| CAS # |
367273-07-2
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| PubChem CID |
9867758
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| Appearance |
White to off-white solid powder
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| Density |
1.4±0.1 g/cm3
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| Boiling Point |
500.9±50.0 °C at 760 mmHg
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| Flash Point |
256.7±30.1 °C
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| Vapour Pressure |
0.0±1.4 mmHg at 25°C
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| Index of Refraction |
1.596
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| LogP |
9.02
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
6
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| Rotatable Bond Count |
3
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| Heavy Atom Count |
30
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| Complexity |
676
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
PNAWUIKCVQSLFG-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H22ClF2NO4/c1-21(2)5-6-22(3,4)16-12(21)9-11(18(27)17(16)23)19(28)26-10-7-13(24)15(20(29)30)14(25)8-10/h7-9,27H,5-6H2,1-4H3,(H,26,28)(H,29,30)
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| Chemical Name |
4-(4-chloro-3-hydroxy-5,5,8,8-tetramethyl-5,6,7,8-tetrahydronaphthalene-2-carboxamido)-2,6-difluorobenzoic acid
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| Synonyms |
NRX195183 NRX-195183 NRX
195183 IRX5183 IRX-5183 IRX 5183VTP-195183 VTP195183 VTP 195183 AGN-195183 AGN195183
AGN195183.
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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 : ~11 mg/mL (~25.12 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 1.1 mg/mL (2.51 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 11.0 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: ≥ 1.1 mg/mL (2.51 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 11.0 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: ≥ 1.1 mg/mL (2.51 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 | 2.2838 mL | 11.4192 mL | 22.8384 mL | |
| 5 mM | 0.4568 mL | 2.2838 mL | 4.5677 mL | |
| 10 mM | 0.2284 mL | 1.1419 mL | 2.2838 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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