| Size | Price | Stock | Qty |
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| 5mg |
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| Targets |
AR antagonist 1 hydrochloride targets the androgen receptor (AR), functioning as a potent antagonist. It binds to AR, preventing its activation by androgens and inhibiting AR-mediated transcription, thereby suppressing androgen-dependent cell proliferation. The compound also binds to E3 ligase ligands with weak binding affinities to VHL protein, making it a valuable building block for the synthesis of PROTAC degraders such as ARD-266. Its dual functionality as an AR antagonist and a ligand for E3 ligase recruitment enables targeted protein degradation applications.
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| ln Vitro |
AR antagonist 1 (compound 29) hydrochloride functions as a ligand for the ARD-266 target ligase. Based on VHL E3 ligase, ARD-266 is an extremely effective androgen receptor (AR) PROTAC degrader [1]. With its E3 ligase complex, AR antagonist 1 exhibits micromolar binding affinity, making it a useful tool for the successful design of PROTAC degraders [1]. Two distinct ligands, one for the E3 ubiquitin ligase and the other for the target protein, are present in PROTAC and are joined by a linker. To specifically break down target proteins, PROTACs make use of the intracellular ubiquitin-proteasome system [1].
In vitro, AR antagonist 1 hydrochloride is a potent androgen receptor antagonist. It binds to AR and prevents its activation by androgens, inhibiting AR-mediated transcription and suppressing androgen-dependent cell proliferation. Its activity is assessed in cell-based assays measuring AR-mediated transcriptional activity using AR-responsive reporter gene constructs. The compound also binds to E3 ligase ligands with weak binding affinities to VHL protein, making it useful for PROTAC synthesis. |
| ln Vivo |
Specific in vivo activity data for AR antagonist 1 hydrochloride as a standalone compound are not extensively documented in the publicly available literature. Its primary application is as a building block for the synthesis of PROTAC ARD-266 rather than as a standalone therapeutic agent. When incorporated into PROTAC molecules, it enables targeted degradation of AR. Further in vivo studies of the standalone compound are needed to characterize its pharmacokinetic and pharmacodynamic properties.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for AR antagonist 1 hydrochloride typically involve competitive binding experiments using androgen receptor and radiolabeled or fluorescently labeled androgen as tracer. The compound's binding affinity to AR is assessed, with IC₅₀ values determined through dose-response binding experiments. Assays are conducted in buffered solutions at physiological pH with appropriate receptor preparations. Its antagonist activity is confirmed through functional assays measuring AR-mediated transcriptional inhibition using AR-responsive reporter gene constructs.
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| Cell Assay |
In vitro cell-based assays for AR antagonist 1 hydrochloride utilize AR-positive prostate cancer cell lines. Cells are treated with varying concentrations of the compound for 24-72 hours. AR-mediated transcriptional activity is evaluated using reporter gene assays with androgen response element (ARE)-luciferase constructs. Cell proliferation is assessed using MTT or CCK-8 assays. The expression of AR target genes such as PSA is measured by qPCR. Standard cell culture conditions (37°C, 5% CO₂) with charcoal-stripped serum are employed to minimize background androgen activity.
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| Animal Protocol |
In vivo animal studies with AR antagonist 1 hydrochloride as a standalone compound are not typically conducted, as its primary application is as a building block for PROTAC synthesis. When incorporated into PROTAC ARD-266, the resulting molecule is evaluated in animal models of prostate cancer. For the standalone compound, potential study designs would include xenograft models using AR-positive cancer cell lines. All procedures must comply with institutional animal care and use guidelines.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for AR antagonist 1 hydrochloride are not extensively documented in the publicly available literature. The compound has a molecular weight of 301.21 g/mol and a molecular formula of C₁₄H₁₈Cl₂N₂O. It is soluble in DMSO at 45 mg/mL. As a small molecule with favorable physicochemical properties, it may have suitable characteristics for oral bioavailability, though detailed PK parameters have not been published. The compound is typically stored under conditions recommended for research chemicals.
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| Toxicity/Toxicokinetics |
AR antagonist 1 hydrochloride is intended for research use only and is not approved for human therapeutic applications. As a research chemical, comprehensive toxicological data are not available in the publicly accessible literature. Standard safety precautions should be observed when handling this compound, including the use of appropriate personal protective equipment. As with all research chemicals, comprehensive toxicological profiling would be required before any consideration for clinical development. The compound should be handled in well-ventilated areas with proper waste disposal procedures.
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| References | |
| Additional Infomation |
AR antagonist 1 hydrochloride (CAS#: 1818885-55-0) is a potent androgen receptor antagonist. It binds to E3 ligase ligands with weak binding affinities to VHL protein and is used in the synthesis of PROTAC ARD-266. As an AR antagonist, it prevents AR activation by androgens and inhibits AR-mediated transcription, suppressing androgen-dependent cell proliferation. This compound is not a drug and has not undergone clinical trials.
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| Molecular Formula |
C15H20CL2N2O
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| Molecular Weight |
315.24
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| Exact Mass |
314.095
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| CAS # |
1818885-55-0
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| Related CAS # |
AR antagonist 1;1818885-54-9
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| PubChem CID |
118435272
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| Appearance |
White to off-white solid powder
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
3
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
20
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| Complexity |
382
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CC1(C(C(C1OC2=CC(=C(C=C2)C#N)Cl)(C)C)N)C.Cl
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| InChi Key |
SHISKTDDIFARGI-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C15H19ClN2O.ClH/c1-14(2)12(18)15(3,4)13(14)19-10-6-5-9(8-17)11(16)7-10;/h5-7,12-13H,18H2,1-4H3;1H
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| Chemical Name |
4-(3-amino-2,2,4,4-tetramethylcyclobutyl)oxy-2-chlorobenzonitrile;hydrochloride
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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: 62.5 mg/mL (198.26 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 | 3.1722 mL | 15.8609 mL | 31.7219 mL | |
| 5 mM | 0.6344 mL | 3.1722 mL | 6.3444 mL | |
| 10 mM | 0.3172 mL | 1.5861 mL | 3.1722 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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