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| Targets |
AGN 194078 is a highly selective agonist of the retinoic acid receptor alpha (RARalpha). It binds to RARalpha with a Kd of 3 nM, demonstrating very high affinity. Its selectivity is remarkable, as it shows no binding to RARbeta and only very weak binding to RARgamma (Kd = 5600 nM). This selective binding activates RARalpha-mediated transcription, with an EC50 of 112 nM. By selectively activating RARalpha, it modulates the expression of target genes involved in cell differentiation, proliferation, and apoptosis.
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| ln Vitro |
AGN 194078 is a selective RARα agonist that binds very weakly (Kd=5600 nM) to RARγ and cannot bind to RARβ. Its Kd value for binding to RARα is 3 nM. Additionally, at the highest tested dose of 1000 nM, AGN 194078 only partially activates RARβ and RARγ, but retains full transcriptional activity through RARα with an EC50 value of 112 nM [1].
In vitro, AGN 194078 is a potent and selective RARalpha agonist. It binds to RARalpha with a Kd of 3 nM and activates the receptor with an EC50 of 112 nM. Its high selectivity for RARalpha over RARbeta and RARgamma makes it a unique tool for dissecting RARalpha-specific signaling pathways. In cell-based reporter assays, it induces RARalpha-mediated transcription in a concentration-dependent manner. It is used to study the specific roles of RARalpha in various cellular processes, including differentiation, development, and cancer. |
| ln Vivo |
In vivo, AGN 194078 is used as a research tool to study the physiological and pathological roles of RARalpha. By selectively activating RARalpha, it can be used to investigate its effects on development, metabolism, and disease in animal models. Its high selectivity reduces the confounding effects associated with pan-RAR agonists, which activate all three RAR subtypes. Specific in vivo efficacy data for AGN 194078 are limited, but it is a valuable tool for probing RARalpha function in vivo.
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| Enzyme Assay |
Cell-free receptor binding assays for AGN 194078 typically use recombinant human RARalpha, RARbeta, and RARgamma proteins. A standard protocol involves incubating the receptor with a radiolabeled ligand (e.g., [3H]-all-trans retinoic acid) and varying concentrations of AGN 194078. Bound and free ligand are separated by charcoal adsorption or filtration, and the radioactivity is measured by scintillation counting. The binding affinity (Kd or Ki) is determined from competitive displacement curves. This assay confirms its high affinity for RARalpha and its selectivity over other RAR subtypes.
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| Cell Assay |
For in vitro cellular experiments, cells expressing RARalpha (e.g., various cancer cell lines or reporter cell lines) are cultured in appropriate media. Cells are treated with AGN 194078 at various concentrations (typically 0.1-1000 nM). RARalpha activation is assessed using a luciferase reporter gene assay, where the receptor drives the expression of a luciferase gene under the control of a retinoic acid response element (RARE). After incubation, a luciferase substrate is added, and the luminescence is measured. The EC50 is calculated from the dose-response curve.
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| Animal Protocol |
In vivo animal experiments with AGN 194078 are typically conducted in mouse models to study the effects of RARalpha activation. A common protocol involves administering the compound via intraperitoneal (IP) or oral (PO) injection at various doses (e.g., 1-10 mg/kg). Tissues are collected, and the expression of RARalpha target genes is assessed by qRT-PCR or Western blotting. The compound's effects on disease progression, such as tumor growth or metabolic parameters, are monitored. Its pharmacokinetic profile and tissue distribution are also studied.
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| ADME/Pharmacokinetics |
AGN 194078 has a molecular weight of 366.34 g/mol and a molecular formula of C22H23F2NO4. It is a small molecule that is likely to have good oral bioavailability due to its lipophilic nature. It is soluble in DMSO. For in vivo studies, it can be formulated in a vehicle such as DMSO, PEG300, or saline. It should be stored as a powder at -20degC, protected from light and moisture. Its pharmacokinetic properties, including half-life and tissue distribution, would need to be characterized for therapeutic development.
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| Toxicity/Toxicokinetics |
The toxicity profile of AGN 194078 has not been extensively characterized. As a potent and selective RARalpha agonist, its toxicity would be related to its mechanism of action. RARalpha agonists can have effects on development, differentiation, and metabolism. Potential toxicities could include effects on the skin, liver, and bone, which are known targets of retinoids. However, its selectivity for RARalpha may reduce some of the side effects associated with pan-RAR agonists. It is for research use only and not for human therapeutic use.
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| References | |
| Additional Infomation |
AGN 194078 is a highly selective RARalpha agonist with a Kd of 3 nM and an EC50 of 112 nM. It shows no binding to RARbeta and only weak binding to RARgamma (Kd = 5600 nM). This remarkable selectivity makes it a valuable research tool for studying RARalpha-specific signaling pathways. It is used to investigate the roles of RARalpha in development, differentiation, and disease. It is not approved for clinical use.
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| Molecular Formula |
C22H23F2NO4
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| Molecular Weight |
403.419133424759
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| Exact Mass |
403.159
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| CAS # |
321995-62-4
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| PubChem CID |
9865875
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| Appearance |
Light yellow to yellow solid powder
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| LogP |
5.8
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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 |
29
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| Complexity |
641
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| Defined Atom Stereocenter Count |
0
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| SMILES |
C(O)(=O)C1=C(F)C=C(NC(C2=C(O)C=C3C(=C2)C(C)(C)CCC3(C)C)=O)C=C1F
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| InChi Key |
BCKLKOYFMACAMZ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C22H23F2NO4/c1-21(2)5-6-22(3,4)14-10-17(26)12(9-13(14)21)19(27)25-11-7-15(23)18(20(28)29)16(24)8-11/h7-10,26H,5-6H2,1-4H3,(H,25,27)(H,28,29)
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| Chemical Name |
2,6-difluoro-4-[(3-hydroxy-5,5,8,8-tetramethyl-6,7-dihydronaphthalene-2-carbonyl)amino]benzoic acid
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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 : ~100 mg/mL (~247.88 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.20 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 25.0 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: ≥ 2.5 mg/mL (6.20 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 25.0 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: ≥ 2.5 mg/mL (6.20 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 | 2.4788 mL | 12.3940 mL | 24.7881 mL | |
| 5 mM | 0.4958 mL | 2.4788 mL | 4.9576 mL | |
| 10 mM | 0.2479 mL | 1.2394 mL | 2.4788 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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