| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
VHL
ARD-266 targets the androgen receptor (AR) for degradation via the ubiquitin-proteasome pathway. As a PROTAC, ARD-266 is a heterobifunctional molecule that contains an AR antagonist (which binds to AR) conjugated to a VHL E3 ligase ligand (which recruits the E3 ubiquitin ligase complex). This brings AR into proximity with the E3 ligase, leading to ubiquitination of AR and subsequent degradation by the proteasome. ARD-266 effectively induces degradation of AR protein in AR-positive prostate cancer cell lines with DC₅₀ values of 0.2-1 nM. |
|---|---|
| ln Vitro |
In LNCaP and VCaP cells, ARD-266 (Compound 11; 100 nM; 1–24 hours) treatment efficiently lowers the level of AR protein in 3 hours and, with a 6-hour treatment, achieves almost total AR elimination[1]. Treatment with ARD-266 (Compound 11; 1–10,000 nM; 24 hours; LNCaP cells) can significantly reduce the mRNA levels of PSA, TMPRSS2, and FKBP5 genes by more than 50% at 10 nM in the LNCaP cell line[1]. It also effectively suppresses the expression of these genes in a dose-dependent manner.
In vitro, ARD-266 effectively induces degradation of AR protein in AR-positive LNCaP, VCaP, and 22Rv1 prostate cancer cell lines with DC₅₀ values of 0.2-1 nM. Specific DC₅₀ values include 0.54 nM in LNCaP, 0.97 nM in VCaP, and 0.15 nM in 22Rv1 cells. The compound's activity is assessed in cell-based assays measuring AR protein levels by Western blot or immunofluorescence following treatment with varying concentrations. Its effects on AR target gene expression and cell proliferation are also evaluated. ARD-266 is a highly potent AR degrader. |
| ln Vivo |
Specific in vivo activity data for ARD-266 are not extensively documented in the publicly available literature. As a PROTAC degrader with potent in vitro activity, the compound has potential applications in prostate cancer research. Its efficacy in vivo would depend on factors such as oral bioavailability, tissue distribution, and target engagement. Further in vivo studies are needed to characterize its pharmacokinetic and pharmacodynamic properties. The compound is for research use only.
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| Enzyme Assay |
In vitro enzyme/receptor binding assays for ARD-266 typically involve assessing its ability to induce degradation of AR protein in cell-based systems rather than direct enzyme binding. The compound's activity is evaluated by measuring AR protein levels using Western blot or immunofluorescence after treatment with varying concentrations. Degradation efficacy is expressed as DC₅₀ values (0.2-1 nM). The compound's ability to recruit VHL E3 ligase can be assessed using ternary complex formation assays. Selectivity for AR over other proteins is confirmed through proteomics analysis.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: LNCaP and VCaP cells Tested Concentrations: 100 nM Incubation Duration: 1 hour, 3 hrs (hours), 6 hrs (hours), 12 hrs (hours), 24 hrs (hours) Experimental Results: Effectively diminished the AR protein level within 3 h and achieved near-complete AR elimination with a 6 h treatment in the LNCaP cells. RT-PCR[1] Cell Types: LNCaP cells Tested Concentrations: 1 nM, 10 nM, 100 nM , 1000 nM, 10000 nM Incubation Duration: 24 hrs (hours) Experimental Results: Effectively suppressed the expression of PSA, TMPRSS2, and FKBP5 genes in a dose-dependent manner and was capable of reducing the mRNA levels of PSA, TMPRSS2, and FKBP5 genes by >50 % at 10 nM in the LNCaP cell line. In vitro cell-based assays for ARD-266 utilize AR-positive prostate cancer cell lines such as LNCaP, VCaP, and 22Rv1. Cells are treated with varying concentrations of the compound for 6-24 hours. AR protein levels are measured by Western blot or high-content imaging to determine DC₅₀ values. AR target gene expression (e.g., PSA, KLK2) is measured by qPCR. Cell proliferation is assessed using MTT or CCK-8 assays. Standard cell culture conditions (37°C, 5% CO₂) with appropriate media are employed. Dose-response curves are generated to determine DC₅₀ and IC₅₀ values. |
| Animal Protocol |
In vivo animal studies with ARD-266 would typically involve administration of the compound to rodent models of prostate cancer, such as xenograft models using AR-positive cell lines. Potential study designs include evaluation of tumor growth inhibition, assessment of AR protein levels in tumor tissues by immunohistochemistry or Western blot, evaluation of AR target gene expression, and pharmacokinetic profiling. All procedures must comply with institutional animal care and use guidelines. Detailed published in vivo protocols are not currently available.
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| ADME/Pharmacokinetics |
ARD-266 has a molecular weight of 915.51 g/mol and a molecular formula of C₅₂H₅₉ClN₆O₇. As a PROTAC molecule, its pharmacokinetic properties may be influenced by its bifunctional nature, which includes both a target-binding moiety and an E3 ligase-recruiting moiety. The compound is typically stored as a powder at -20°C. Information concerning product stability, particularly in solution, has rarely been reported. Further studies are needed to characterize its pharmacokinetic profile.
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| Toxicity/Toxicokinetics |
ARD-266 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 |
ARD-266 (CAS#: 2666951-70-6) is a highly potent VHL E3 ligase-based PROTAC androgen receptor degrader with DC₅₀ values of 0.2-1 nM in AR-positive prostate cancer cell lines. It contains an AR antagonist conjugated to a VHL ligand via a piperidine-alkyne linker. ARD-266 effectively induces AR protein degradation in LNCaP, VCaP, and 22Rv1 cells. This compound is not a drug and has not undergone clinical trials.
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| Molecular Formula |
C52H59CLN6O7
|
|---|---|
| Molecular Weight |
915.513872385025
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| Exact Mass |
914.413
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| CAS # |
2666951-70-6
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| PubChem CID |
145996519
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| Appearance |
White to off-white solid powder
|
| LogP |
7.6
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| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
9
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| Rotatable Bond Count |
13
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| Heavy Atom Count |
66
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| Complexity |
1830
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| Defined Atom Stereocenter Count |
4
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| SMILES |
CC1=NOC(=C1)[C@@H](C(C)C)C(=O)N2C[C@@H](C[C@H]2C(=O)N[C@@H](CC(=O)N3CCC(CC3)C#CC4=CC=C(C=C4)C(=O)NC5C(C(C5(C)C)OC6=CC(=C(C=C6)C#N)Cl)(C)C)C7=CC=CC=C7)O
|
| InChi Key |
RTNONCBKGZNCJS-WPVVNVAYSA-N
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| InChi Code |
InChI=1S/C52H59ClN6O7/c1-31(2)45(43-25-32(3)57-66-43)48(64)59-30-38(60)26-42(59)47(63)55-41(35-11-9-8-10-12-35)28-44(61)58-23-21-34(22-24-58)14-13-33-15-17-36(18-16-33)46(62)56-49-51(4,5)50(52(49,6)7)65-39-20-19-37(29-54)40(53)27-39/h8-12,15-20,25,27,31,34,38,41-42,45,49-50,60H,21-24,26,28,30H2,1-7H3,(H,55,63)(H,56,62)/t38-,41+,42+,45-,49?,50?/m1/s1
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| Chemical Name |
(2S,4R)-N-[(1S)-3-[4-[2-[4-[[3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]carbamoyl]phenyl]ethynyl]piperidin-1-yl]-3-oxo-1-phenylpropyl]-4-hydroxy-1-[(2R)-3-methyl-2-(3-methyl-1,2-oxazol-5-yl)butanoyl]pyrrolidine-2-carboxamide
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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 (109.23 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (5.46 mM) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% 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 50.0 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: 5 mg/mL (5.46 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 ultrasonication. For example, if 1 mL of working solution is to be prepared, you can add 100 μL of 50.0 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: ≥ 5 mg/mL (5.46 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 | 1.0923 mL | 5.4614 mL | 10.9229 mL | |
| 5 mM | 0.2185 mL | 1.0923 mL | 2.1846 mL | |
| 10 mM | 0.1092 mL | 0.5461 mL | 1.0923 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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