| Size | Price | Stock | Qty |
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| Targets |
ARD-2585 targets the Androgen Receptor (AR) for degradation. It is a PROTAC molecule that simultaneously binds to AR and an E3 ubiquitin ligase (likely VHL), leading to the ubiquitination and subsequent proteasomal degradation of the AR protein. This eliminates both the full-length receptor and its splice variants.
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| ln Vitro |
In the VCaP cell line with AR gene amplification and the LNCaP cell line with AR mutation, ARD-2585 has a DC50 value of 0.04 ~ 0.1 nM [1]. AR protein levels can be lowered by 78% at 3 and 24 hours (p < 0.01) and by 60% at 6 hours (p > 0.05) with ARD-2585 (100 nM) [1].
In vitro, ARD-2585 is effective in reducing AR protein levels. In cell-based degradation assays, it achieves 78% reduction in AR levels at 3 hours and 60% reduction at 6 hours. This rapid and potent depletion of AR protein leads to a more profound and sustained blockade of AR-driven gene transcription compared to standard antagonists. |
| ln Vivo |
ARD-2585 is an orally active PROTAC degrader that demonstrates in vivo efficacy in animal models of advanced prostate cancer. By driving the complete degradation of AR, it can overcome resistance mechanisms that arise from mutations or overexpression in the ligand-binding domain, making it a powerful research tool for studying AR-dependent malignancies.
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| Enzyme Assay |
Cell-free degradation assays are performed using purified components. The PROTAC ternary complex formation is assessed by incubating ARD-2585 with purified AR and the VHL E3 ligase complex. Binding is measured via SPR or by a fluorescence polarization-based assay that detects the formation of the ternary complex, which is the first step of the degradation cascade.
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| Cell Assay |
Cellular degradation assays are performed in AR+ prostate cancer cell lines (e.g., LNCaP, VCaP). Cells are treated with a concentration range of ARD-2585 for 3-6 hours. Cells are harvested, lysed, and AR protein levels are measured by Western blot. The DC50 value, the concentration required for 50% protein degradation, is calculated by densitometry. The time course of degradation is also evaluated.
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| Animal Protocol |
In vivo efficacy studies are conducted in mice bearing AR+ prostate cancer xenografts, including models of enzalutamide resistance. ARD-2585 is administered orally once daily. Tumor growth is measured with calipers. At study termination, tumors are harvested and analyzed for AR protein levels by Western blot and IHC to confirm target degradation in vivo.
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| ADME/Pharmacokinetics |
ARD-2585 is an orally bioavailable PROTAC, a key advantage for therapeutic research. Its pharmacokinetic profile is optimized to achieve systemic exposure that is sufficient to drive tumor AR degradation. The compound's properties support once-daily oral dosing in preclinical animal models.
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| Toxicity/Toxicokinetics |
Preclinical toxicology studies for ARD-2585 are ongoing. As a protein degrader, its safety profile will be determined by its selectivity for the target AR and the pharmacology of AR degradation. On-target toxicities may include the effects of androgen deprivation. Off-target toxicities are a focus of lead optimization efforts for PROTACs.
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| References | |
| Additional Infomation |
ARD-2585 is a next-generation research agent designed to address the shortcomings of traditional AR antagonists. By degrading the receptor rather than just blocking it, it has the potential to provide therapeutic benefit in prostate cancer patients who have acquired resistance to first-line therapies. It is a research compound and has not been approved for clinical use.
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| Molecular Formula |
C41H43CLN8O5
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|---|---|
| Molecular Weight |
763.28
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| Exact Mass |
762.304
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| CAS # |
2757422-79-8
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| PubChem CID |
162366967
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| Appearance |
Light yellow to green yellow solid powder
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| Density |
1.46±0.1 g/cm3(Predicted)
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| Boiling Point |
1032.7±65.0 °C(Predicted)
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| LogP |
4.5
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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 |
8
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| Heavy Atom Count |
55
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| Complexity |
1520
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| Defined Atom Stereocenter Count |
0
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| SMILES |
CN(C1CCC(CC1)NC(=O)C2=CC=C(C=C2)N3CCN(CC3)C4CN(C4)C5=CC6=C(C=C5)C(=O)N(C6=O)C7CCC(=O)NC7=O)C8=CC(=C(C=C8)C#N)Cl
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| InChi Key |
LUCHABJUYSYJAT-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C41H43ClN8O5/c1-46(30-9-4-26(22-43)35(42)21-30)28-10-5-27(6-11-28)44-38(52)25-2-7-29(8-3-25)47-16-18-48(19-17-47)32-23-49(24-32)31-12-13-33-34(20-31)41(55)50(40(33)54)36-14-15-37(51)45-39(36)53/h2-4,7-9,12-13,20-21,27-28,32,36H,5-6,10-11,14-19,23-24H2,1H3,(H,44,52)(H,45,51,53)
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| Chemical Name |
N-[4-(3-chloro-4-cyano-N-methylanilino)cyclohexyl]-4-[4-[1-[2-(2,6-dioxopiperidin-3-yl)-1,3-dioxoisoindol-5-yl]azetidin-3-yl]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: 85 mg/mL (111.36 mM)
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|---|---|
| Solubility (In Vivo) |
Solubility in Formulation 1: 4.25 mg/mL (5.57 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 42.5 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: ≥ 4.25 mg/mL (5.57 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 42.5 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. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 1.3101 mL | 6.5507 mL | 13.1014 mL | |
| 5 mM | 0.2620 mL | 1.3101 mL | 2.6203 mL | |
| 10 mM | 0.1310 mL | 0.6551 mL | 1.3101 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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