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| Targets |
The primary target of AGN 196996 is the retinoic acid receptor alpha (RARα). It functions as a potent and selective antagonist of this nuclear receptor. The compound binds to RARα with a very high affinity, as indicated by a Ki value of 2 nM. In contrast, it exhibits very low affinity for RARβ (Ki = 1087 nM) and RARγ (Ki = 8523 nM). This high degree of selectivity is a key feature of AGN 196996. RARα is a nuclear receptor that is activated by retinoic acid, the active metabolite of vitamin A. Upon activation, RARα forms heterodimers with retinoid X receptors (RXRs) and binds to retinoic acid response elements (RAREs) in the DNA, regulating the transcription of target genes involved in cell growth, differentiation, and apoptosis.
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| ln Vitro |
In vitro, AGN 196996 functions as an antagonist, blocking the gene transcriptional activity induced by all-trans retinoic acid (ATRA) and other RAR agonists. It shows no activity in transactivation assays on its own, confirming its role as a pure antagonist. Studies have shown that antagonists of retinoic acid receptors, including AGN 196996, are potent growth inhibitors of prostate carcinoma cells. The compound's high selectivity for RARα allows researchers to study the specific contribution of this receptor subtype to the effects of retinoic acid, without the confounding effects of blocking RARβ or RARγ.
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| ln Vivo |
In vivo, AGN 196996 has been evaluated in preclinical models for its anticancer activity. It has been reported to more effectively inhibit the growth of human prostate cancer cells than normal prostate epithelium. This suggests that RARα antagonists like AGN 196996 may have a therapeutic window for treating prostate cancer. By blocking RARα, the compound can inhibit the growth of cancer cells that are dependent on RARα signaling. Further in vivo studies are needed to fully characterize its efficacy and safety profile. The compound is not approved for human use and is strictly a research tool.
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| Enzyme Assay |
For in vitro receptor binding assays, the affinity of AGN 196996 for RARα, RARβ, and RARγ is determined using radioligand binding assays. These assays involve incubating the receptor protein with a radiolabeled ligand (e.g., [³H]ATRA) and varying concentrations of the test compound. The amount of radioligand bound to the receptor is measured, and competition curves are generated to calculate the Ki values. The high selectivity of AGN 196996 for RARα is confirmed by its much lower affinity for the other subtypes.
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| Cell Assay |
For in vitro cell-based assays, the functional activity of AGN 196996 is assessed using reporter gene assays. Cells are transfected with a plasmid containing a luciferase reporter gene driven by a retinoic acid response element (RARE) and an expression plasmid for RARα. The cells are then treated with a RAR agonist like ATRA in the presence or absence of the compound. The antagonist activity is measured by the compound's ability to inhibit the ATRA-induced luciferase activity. The compound's effects on cell proliferation can be evaluated using cancer cell lines, such as prostate cancer cells. Cell viability is measured using MTT or CCK-8 assays.
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| Animal Protocol |
For in vivo animal studies, AGN 196996 is typically administered orally or intraperitoneally. Xenograft models of cancer, such as human prostate cancer cells implanted in immunocompromised mice, are used to evaluate its antitumor efficacy. Tumor-bearing mice are treated with the compound, and tumor growth is monitored. The compound can be formulated in a vehicle such as 10% DMSO in corn oil. At the end of the study, tumors are collected for histology and molecular analysis to assess the mechanism of action.
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| ADME/Pharmacokinetics |
Pharmacokinetic properties of AGN 196996: The compound has a molecular weight of 482.32 and is soluble in DMSO (250 mg/mL). For in vivo administration, a formulation of 10% DMSO in corn oil can be used. Detailed pharmacokinetic parameters, such as half-life, bioavailability, and tissue distribution, are not extensively available in the public literature. As a small, lipophilic molecule, it is expected to have reasonable oral bioavailability.
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| Toxicity/Toxicokinetics |
Specific toxicity data for AGN 196996 are limited. The compound is used as a research tool and is not intended for human therapeutic use. As a potent RARα antagonist, it may have effects on normal tissues that depend on RARα signaling, such as skin and bone. Comprehensive toxicological studies have not been published. Standard laboratory safety precautions should be observed when handling the compound.
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| References |
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| Additional Infomation |
AGN 196996 is a research compound with no clinical trial or regulatory approval status. It is a potent and highly selective RARα antagonist used as a pharmacological tool to study RARα-mediated signaling pathways. It is commercially available from chemical suppliers for research purposes only. The compound is valuable for investigating the role of RARα in cancer, development, and differentiation.
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| Molecular Formula |
C24H20BRNO5
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| Molecular Weight |
482.323306083679
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| Exact Mass |
481.052
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| CAS # |
958295-17-5
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| PubChem CID |
24785198
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| Appearance |
White to off-white solid powder
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| Density |
1.453±0.06 g/cm3 (20 °C, 760 mmHg)
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| Boiling Point |
619.8±55.0 °C (760 mmHg)
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| LogP |
5.41
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
7
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| Heavy Atom Count |
31
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| Complexity |
640
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CCOC1=C(C=C(C=C1Br)C(=O)NC2=CC=C(C=C2)C(=O)O)C(=O)C3=CC=C(C=C3)C
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| InChi Key |
BUGXGZOGQGUTBC-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C24H20BrNO5/c1-3-31-22-19(21(27)15-6-4-14(2)5-7-15)12-17(13-20(22)25)23(28)26-18-10-8-16(9-11-18)24(29)30/h4-13H,3H2,1-2H3,(H,26,28)(H,29,30)
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| Chemical Name |
4-[[3-bromo-4-ethoxy-5-(4-methylbenzoyl)benzoyl]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 : ~250 mg/mL (~518.33 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 2.08 mg/mL (4.31 mM) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (add these co-solvents sequentially from left to right, and one by one), suspension solution; with sonication.
For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 20.8 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. Solubility in Formulation 2: ≥ 2.08 mg/mL (4.31 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 20.8 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.0733 mL | 10.3666 mL | 20.7331 mL | |
| 5 mM | 0.4147 mL | 2.0733 mL | 4.1466 mL | |
| 10 mM | 0.2073 mL | 1.0367 mL | 2.0733 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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