| Size | Price | Stock | Qty |
|---|---|---|---|
| 1mg |
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| Other Sizes |
| Targets |
Androgen receptor (AR) and VHL E3 ubiquitin ligase. ARD-69 binds to the AR ligand-binding domain and the VHL E3 ligase, recruiting AR to the E3 complex, inducing its ubiquitination and subsequent proteasomal degradation, thereby blocking AR signaling and downstream gene expression.
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|---|---|
| ln Vitro |
ARD-69 induces potent and dose-dependent degradation of AR protein in AR-positive prostate cancer cell lines (e.g., LNCaP, VCaP, 22Rv1) with DC50 values in the low nanomolar range (1-10 nM). It inhibits AR-regulated gene expression (PSA, TMPRSS2) and suppresses cell proliferation at sub-micromolar concentrations.
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| ln Vivo |
ARD-69 has not been extensively evaluated in animal models; however, as a highly potent PROTAC, it is expected to degrade AR in vivo, leading to tumor growth inhibition in AR-positive xenograft models. Oral administration of similar AR PROTACs (e.g., ARD-61) has shown efficacy in mice.
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| Enzyme Assay |
Recombinant AR ligand-binding domain (AR-LBD, 10-50 nM) and VHL protein (10-50 nM) are incubated with ARD-69 (0.1-1000 nM) in TR-FRET assay buffer (50 mM HEPES, pH 7.4, 150 mM NaCl, 0.01% Tween 20) for 1-2 hours at room temperature. Ternary complex formation is measured by time-resolved FRET using labeled anti-GST and anti-His antibodies.
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| Cell Assay |
AR-positive LNCaP or VCaP cells are treated with ARD-69 (0.1-1000 nM) for 4-24 hours. AR protein levels are measured by Western blot and quantified relative to beta-actin. DC50 (concentration for 50% degradation) is calculated from dose-response curves. Cell proliferation is assessed after 72-96 hours by CellTiter-Glo.
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| Animal Protocol |
Not yet reported for ARD-69. For similar AR PROTACs, mice bearing LNCaP xenografts are treated with 10-50 mg/kg (oral or IP) once daily for 3-4 weeks. Tumors are collected, and AR protein levels are measured by Western blot. Tumor growth inhibition (TGI) is calculated.
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| ADME/Pharmacokinetics |
No published PK data for ARD-69. Based on its high molecular weight (1129.8 Da), PROTACs generally have poor oral bioavailability (F <10%) and a short plasma half-life (1-3 hours) due to rapid clearance. Administration via intraperitoneal injection or subcutaneous is preferred.
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| Toxicity/Toxicokinetics |
No formal toxicity data. PROTACs can exhibit off-target degradation of related proteins. In cell lines, ARD-69 shows no significant cytotoxicity at DC50 concentrations. Toxicological assessment would be required for in vivo applications. Handle with care as with all PROTAC molecules.
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| References | |
| Additional Infomation |
ARD-69 is a research tool for PROTAC development, not FDA-approved. It demonstrates the utility of the PROTAC approach for targeting AR in castration-resistant prostate cancer (CRPC), including AR splice variants. ARD-69 is a valuable tool for studying AR degradation mechanisms and overcoming resistance to AR antagonists.
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| Molecular Formula |
C62H74CLFN8O7S
|
|---|---|
| Molecular Weight |
1129.81677675247
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| Exact Mass |
1128.507
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| CAS # |
2316837-10-0
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| Related CAS # |
2316837-10-0;
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| PubChem CID |
137321163
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| Appearance |
White to off-white solid powder
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| LogP |
9.3
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| Hydrogen Bond Donor Count |
4
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| Hydrogen Bond Acceptor Count |
12
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| Rotatable Bond Count |
16
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| Heavy Atom Count |
80
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| Complexity |
2350
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| Defined Atom Stereocenter Count |
4
|
| SMILES |
ClC1=C(C#N)C=CC(=C1)OC1C(C)(C)C(C1(C)C)NC(C1C=CC(C#CC2CCN(CC2)C2CCN(C(C[C@@H](C3C=CC(C4=C(C)N=CS4)=CC=3)NC([C@@H]3C[C@H](CN3C([C@H](C(C)(C)C)NC(C3(CC3)F)=O)=O)O)=O)=O)CC2)=CC=1)=O
|
| InChi Key |
CWGVEMFBQJUWLU-SKTBPLDYSA-N
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| InChi Code |
InChI=1S/C62H74ClFN8O7S/c1-37-51(80-36-66-37)41-17-15-40(16-18-41)48(67-54(76)49-31-45(73)35-72(49)55(77)52(59(2,3)4)68-58(78)62(64)25-26-62)33-50(74)71-29-23-44(24-30-71)70-27-21-39(22-28-70)10-9-38-11-13-42(14-12-38)53(75)69-56-60(5,6)57(61(56,7)8)79-46-20-19-43(34-65)47(63)32-46/h11-20,32,36,39,44-45,48-49,52,56-57,73H,21-31,33,35H2,1-8H3,(H,67,76)(H,68,78)(H,69,75)/t45-,48+,49+,52-,56?,57?/m1/s1
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| Chemical Name |
(2S,4R)-N-[(1S)-3-[4-[4-[2-[4-[[3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]carbamoyl]phenyl]ethynyl]piperidin-1-yl]piperidin-1-yl]-1-[4-(4-methyl-1,3-thiazol-5-yl)phenyl]-3-oxopropyl]-1-[(2S)-2-[(1-fluorocyclopropanecarbonyl)amino]-3,3-dimethylbutanoyl]-4-hydroxypyrrolidine-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 Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage. (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture. |
| 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 : ≥ 200 mg/mL (~177.02 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 | 0.8851 mL | 4.4255 mL | 8.8510 mL | |
| 5 mM | 0.1770 mL | 0.8851 mL | 1.7702 mL | |
| 10 mM | 0.0885 mL | 0.4425 mL | 0.8851 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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