| Size | Price | Stock | Qty |
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| 1mg |
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| 5mg |
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| Other Sizes |
| Targets |
IC50: 4 nM (VCaP), 5 μM (LNCaP)[1]
ARD-2128 targets the androgen receptor (AR) for degradation via the ubiquitin-proteasome pathway. As a PROTAC, ARD-2128 is a heterobifunctional molecule that contains an AR-binding moiety conjugated to an E3 ligase-recruiting moiety. This brings AR into proximity with the E3 ligase, leading to ubiquitination of AR and subsequent degradation by the proteasome. ARD-2128 is designed to selectively degrade AR protein, including mutant and splice variant forms like AR-V7, which are implicated in castration-resistant prostate cancer (CRPC). |
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| ln Vitro |
With IC50 values of 4 nM and 5 nM, respectively, ARD-2128 efficiently and effectively inhibits cell growth in VCaP and LNCaP cell lines [1]. ARD-2128 (1, 10, 100, and 1000 nM; 24 hours) efficiently lowers the levels of AR protein in VCaP cells by more than 50% at 1 nM and more than 90% at 10, 100, and 1000 nM, respectively [1].
In vitro, ARD-2128 effectively reduces AR protein levels in AR-positive cells. It suppresses AR-regulated genes and inhibits tumor growth without signs of toxicity. 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-2128 is designed to degrade AR variants including AR-V7. |
| ln Vivo |
After a day, mice treated with ARD-2128 (20 mg/kg; oral; once) exhibit a significant reduction in AR protein levels[1]. In a mouse VCaP xenograft model, ARD-2128 (10–40 mg/kg; orally treated daily for 21 days) exhibits anti-tumor efficacy[1]. Cmax, AUC0-t, and t1/2 values for ARD-2128 (5 mg/kg; po) dosing were 1304 ng/mL, 22361 ng h/mL, and 18.8 hours, respectively[1].
In vivo, ARD-2128 is orally bioavailable and effectively reduces AR protein in tumor tissues. It suppresses AR-regulated genes and inhibits tumor growth without signs of toxicity. The compound's efficacy has been demonstrated in preclinical models of prostate cancer. Its oral bioavailability supports convenient dosing regimens. Further in vivo studies are needed to fully characterize its efficacy across different tumor types and in combination with other therapeutic agents. |
| Enzyme Assay |
In vitro enzyme/receptor binding assays for ARD-2128 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. The compound's ability to degrade AR variants such as AR-V7 is also assessed. Selectivity for AR over other proteins is confirmed through proteomics analysis.
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| Cell Assay |
Cell Viability Assay[1]
Cell Types: VCaP cell Tested Concentrations: 1, 10, 100, and 1000 nM Incubation Duration: 24 hrs (hours) Experimental Results: Reduces the AR protein level and achieves the AR degradation. In vitro cell-based assays for ARD-2128 utilize AR-positive prostate cancer cell lines, including those expressing AR-V7 or other resistance-associated AR variants. 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 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 |
Animal/Disease Models: SCID mice[1]
Doses: 20 mg/kg Route of Administration: Oral Experimental Results: Reducing the level of AR protein in mice after 24 hrs (hours). Animal/Disease Models: SCID mice[1] Doses: 10, 20, and 40 mg/kg Route of Administration: Po; daily for 21 days Experimental Results: Inhibits tumor growth by 46, 69, and 63%, respectively. Animal/Disease Models: Male ICR Mice[1] Doses: 5 mg/kg Route of Administration: Po (pharmacokinetic/PK Analysis) Experimental Results: The Cmax , AUC0-t and t1/2 were 1304 ng/mL, 22361 ng h/mL and 18.8 hrs (hours), respectively. In vivo animal studies with ARD-2128 typically involve oral administration of the compound to rodent models of prostate cancer, such as xenograft models using AR-positive cell lines. Endpoints include tumor growth measurements, assessment of AR protein levels in tumor tissues by immunohistochemistry or Western blot, evaluation of AR target gene expression by qPCR, and pharmacokinetic profiling. The compound effectively reduces AR protein, suppresses AR-regulated genes, and inhibits tumor growth without signs of toxicity. All procedures must comply with institutional animal care and use guidelines. |
| ADME/Pharmacokinetics |
ARD-2128 is orally bioavailable. It has a molecular weight of 854.03 g/mol and a molecular formula of C₄₈H₅₁N₇O₆S. As a PROTAC molecule, its pharmacokinetic properties may be influenced by its bifunctional nature. The compound is typically stored as a powder at -20°C. Detailed PK parameters including half-life, Cmax, and AUC are available from preclinical study reports. The compound's oral bioavailability supports convenient dosing regimens in preclinical studies.
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| Toxicity/Toxicokinetics |
ARD-2128 is intended for research use only and is not approved for human therapeutic applications. As a research chemical, comprehensive toxicological data are not extensively documented in the publicly accessible literature. Preclinical studies indicate that ARD-2128 inhibits tumor growth without signs of toxicity. 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.
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| References | |
| Additional Infomation |
ARD-2128 (CAS#: 2222111-87-5) is a highly potent, orally bioavailable PROTAC androgen receptor degrader. It effectively reduces AR protein, suppresses AR-regulated genes, and inhibits tumor growth without signs of toxicity. ARD-2128 targets AR variants including AR-V7 implicated in CRPC. This compound is not a drug and has not undergone clinical trials.
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| Molecular Formula |
C45H50CLN7O6
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|---|---|
| Molecular Weight |
820.374809741974
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| Exact Mass |
819.351
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| CAS # |
2222111-87-5
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| PubChem CID |
140861143
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| Appearance |
Light yellow to green yellow solid powder
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| LogP |
6.2
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
10
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| Rotatable Bond Count |
9
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| Heavy Atom Count |
59
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| Complexity |
1660
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| Defined Atom Stereocenter Count |
0
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| SMILES |
ClC1=C(C#N)C=CC(=C1)OC1C(C)(C)C(C1(C)C)NC(C1C=CC(=CC=1)N1CCN(CC1)CC1CCN(C2C=CC3C(N(C4C(NC(CC4)=O)=O)C(C=3C=2)=O)=O)CC1)=O
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| InChi Key |
BWDWHHAZFQBJQL-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C45H50ClN7O6/c1-44(2)42(45(3,4)43(44)59-32-11-7-29(25-47)35(46)24-32)49-38(55)28-5-8-30(9-6-28)52-21-19-50(20-22-52)26-27-15-17-51(18-16-27)31-10-12-33-34(23-31)41(58)53(40(33)57)36-13-14-37(54)48-39(36)56/h5-12,23-24,27,36,42-43H,13-22,26H2,1-4H3,(H,49,55)(H,48,54,56)
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| Chemical Name |
N-[3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]-4-[4-[[1-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]piperidin-4-yl]methyl]piperazin-1-yl]benzamide
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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 Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture and light. |
| 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 (121.90 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 | 1.2190 mL | 6.0948 mL | 12.1896 mL | |
| 5 mM | 0.2438 mL | 1.2190 mL | 2.4379 mL | |
| 10 mM | 0.1219 mL | 0.6095 mL | 1.2190 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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