| Size | Price | Stock | Qty |
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| Targets |
ARCC-4 targets the androgen receptor (AR), a nuclear hormone receptor that plays a critical role in prostate cancer progression. It is a PROTAC (proteolysis-targeting chimera) that recruits the von Hippel-Lindau (VHL) E3 ligase to the androgen receptor, leading to its ubiquitination and subsequent degradation by the proteasome. ARCC-4 selectively degrades AR via the proteasome but not PR-A or PR-B.
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| ln Vitro |
The three-promoted polymer complex binds more readily when ARCC-4 improves the protein-protein reaction between AR and VHL [1]. AR can be efficiently degraded by -4 (0.1-10,000 nM; 20 hours), with a D50 of 5 nM and a Dmax of greater than 95% [1]. Molds with ARCC-4 (100 nM; 12 hours) exhibit AR. ARCC-4 does not impede PR-A or PR-B, but it nearly solely modulates AR through chromoplast pigments [1]. Clinically significant AR mutations are effectively suppressed by ARCC-4 [1]. ARCC-4 is still functional in the presence of high androgen levels [1].
In vitro, ARCC-4 degrades about 95% of cellular androgen receptors. It has a DC50 of 5 nM. ARCC-4 inhibits prostate tumor cell proliferation, degrades clinically relevant AR point mutants, and retains antiproliferative effect in a high androgen environment, unlike enzalutamide. It is based on enzalutamide and incorporates a VHL E3 ligase ligand. |
| ln Vivo |
In vivo, ARCC-4 shows efficacy against clinically relevant AR mutations and maintains activity despite elevated androgen levels. It inhibits prostate tumor cell proliferation in preclinical models. However, specific details of in vivo studies, such as the animal models used and the dosing regimens, are not extensively detailed in the available literature.
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| Enzyme Assay |
The in vitro binding assay for ARCC-4 measures its ability to bind to the androgen receptor and recruit the VHL E3 ligase. These cell-free assays typically use purified proteins or cell lysates to assess the formation of the ternary complex. The compound's ability to induce AR ubiquitination can also be assessed in cell-free systems. These assays provide a direct measure of the compound's mechanism of action.
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| Cell Assay |
Western Blot Analysis[1]
Cell Types: VCaP cells Tested Concentrations: 0.1 nM, 1 nM, 10 nM, 50 nM, 100 nM, 0.5μM, 1μM. , 10 μM Incubation Duration: 20 hrs (hours) Experimental Results: Effective degradation of AR In vitro cellular assays for ARCC-4 assess its ability to degrade the androgen receptor and inhibit cell proliferation. Prostate cancer cell lines are treated with various concentrations of ARCC-4, and AR protein levels are measured by Western blot to determine the DC50. Cell proliferation is assessed using cell viability assays. These assays demonstrate the compound's ability to degrade AR and inhibit prostate tumor cell proliferation. |
| Animal Protocol |
In vivo animal studies for ARCC-4 are conducted in mouse xenograft models of prostate cancer. Tumor-bearing mice are treated with ARCC-4, and tumor growth is monitored. The compound's ability to inhibit tumor growth and degrade AR in vivo is assessed. These studies demonstrate the compound's in vivo efficacy against prostate cancer. However, specific details are not extensively detailed in the available literature.
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| ADME/Pharmacokinetics |
Specific pharmacokinetic data for ARCC-4 are not extensively detailed in the available literature. As a PROTAC, its pharmacokinetic properties are important for its in vivo efficacy. However, specific parameters such as oral bioavailability, half-life, and distribution are not provided. The compound is primarily used in research settings.
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| Toxicity/Toxicokinetics |
Specific toxicity data for ARCC-4 are not extensively detailed in the available literature. As a PROTAC targeting the androgen receptor, its toxicity profile is likely related to its mechanism of action. However, preclinical toxicology studies would be required to assess its safety margin. The compound is intended for research use only and is not for human use.
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| References | |
| Additional Infomation |
ARCC-4 is a low-nanomolar androgen receptor degrader based on PROTAC technology. It has a DC50 of 5 nM and is an enzalutamide-based VHL-recruiting AR PROTAC. ARCC-4 selectively degrades AR via the proteasome, inhibits prostate tumor cell proliferation, and retains activity against clinically relevant AR mutations and in high androgen environments. It is a research compound for studying AR degradation in prostate cancer.
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| Molecular Formula |
C53H58F3N7O8S2
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| Molecular Weight |
1042.19494104385
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| Exact Mass |
1023.363
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| CAS # |
1973403-00-7
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| Related CAS # |
1973403-00-7;ARCC-4 hydrate;
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| PubChem CID |
122428515
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| Appearance |
White to off-white solid powder
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| LogP |
8.5
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| Hydrogen Bond Donor Count |
3
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| Hydrogen Bond Acceptor Count |
14
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| Rotatable Bond Count |
18
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| Heavy Atom Count |
72
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| Complexity |
1940
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| Defined Atom Stereocenter Count |
3
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| SMILES |
S=C1N(C2C=CC(C#N)=C(C(F)(F)F)C=2)C(C(C)(C)N1C1C=CC(C2C=CC(=CC=2)OCCCCOCC(N[C@H](C(N2C[C@@H](C[C@H]2C(NCC2C=CC(C3=C(C)N=CS3)=CC=2)=O)O)=O)C(C)(C)C)=O)=CC=1)=O.O
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| InChi Key |
DUPAJELXESPTNF-PPZGWQTASA-N
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| InChi Code |
InChI=1S/C53H56F3N7O7S2/c1-32-45(72-31-59-32)36-11-9-33(10-12-36)28-58-47(66)43-26-40(64)29-61(43)48(67)46(51(2,3)4)60-44(65)30-69-23-7-8-24-70-41-21-16-35(17-22-41)34-13-18-38(19-14-34)63-50(71)62(49(68)52(63,5)6)39-20-15-37(27-57)42(25-39)53(54,55)56/h9-22,25,31,40,43,46,64H,7-8,23-24,26,28-30H2,1-6H3,(H,58,66)(H,60,65)/t40-,43+,46-/m1/s1
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| Chemical Name |
(2S,4R)-1-[(2S)-2-[[2-[4-[4-[4-[3-[4-cyano-3-(trifluoromethyl)phenyl]-5,5-dimethyl-4-oxo-2-sulfanylideneimidazolidin-1-yl]phenyl]phenoxy]butoxy]acetyl]amino]-3,3-dimethylbutanoyl]-4-hydroxy-N-[[4-(4-methyl-1,3-thiazol-5-yl)phenyl]methyl]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 : ~200 mg/mL (~195.28 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: 5 mg/mL (4.88 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 (4.88 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 (4.88 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 | 0.9595 mL | 4.7975 mL | 9.5951 mL | |
| 5 mM | 0.1919 mL | 0.9595 mL | 1.9190 mL | |
| 10 mM | 0.0960 mL | 0.4798 mL | 0.9595 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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