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| 1mg |
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| Targets |
Androgen receptor antagonist 1 targets the androgen receptor (AR), a nuclear receptor that mediates the effects of androgens such as testosterone and dihydrotestosterone. By binding to the AR ligand-binding domain, the compound prevents androgen-induced AR activation and transcriptional activity. It is a full antagonist, meaning it completely blocks AR signaling. The compound can also be used as a ligand for PROTACs, where it recruits AR to E3 ubiquitin ligases for degradation. This dual function—antagonism and degradation—makes it a powerful tool for studying AR biology and for therapeutic development in prostate cancer.
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| ln Vitro |
Androgen receptor antagonist 1 (compound 26) had notable cytostatic effects on LNCaP and LNAR cells, while having no effect on DU145 cells [1].
Androgen receptor antagonist 1 exhibits potent in vitro activity as an AR antagonist. Its IC50 of 59 nM indicates high potency. In cell-based reporter assays, the compound inhibits AR-mediated transcriptional activity in a dose-dependent manner. It effectively blocks the growth of AR-positive prostate cancer cell lines such as LNCaP. When used as a PROTAC ligand, androgen receptor antagonist 1 induces AR degradation in LNCaP cells, with 24% degradation at 1 µM and 47% at 10 µM. These in vitro activities confirm its utility as a research tool for studying AR signaling and degradation. |
| ln Vivo |
In an animal model of castration-resistant prostate cancer (CRPC), androgen receptor antagonist 1 (Compound 26; 100 mg/kg once daily for 5 weeks) showed good in vivo tumor growth reduction following oral administration [ 1].
In vivo activity of androgen receptor antagonist 1 has been evaluated in animal models of prostate cancer. As an orally available compound, it can be administered to mice to study its effects on AR signaling and tumor growth. In xenograft models using AR-positive prostate cancer cells, the compound has shown efficacy in inhibiting tumor growth. When used in PROTAC AR degraders, it has demonstrated potent AR degradation in vivo. These studies support its potential as a therapeutic agent for prostate cancer. |
| Enzyme Assay |
In vitro receptor binding assays for androgen receptor antagonist 1 involve measuring its affinity for the androgen receptor. Competitive binding assays using radiolabeled androgens (e.g., [3H]-DHT) are commonly used. The compound is incubated with AR and the radioligand, and the displacement is measured to calculate the IC50 (59 nM). Transactivation assays using AR-responsive luciferase reporters are used to measure functional antagonism. These assays confirm the compound’s mechanism as an AR antagonist.
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| Cell Assay |
Cell proliferation assay[1]
Cell Types: Prostate cancer (CaP) cells (LNCAP, LNAR and DU145) Tested Concentrations: 1 nM, 10 nM, 100 nM, 1 μM, 10 μM, 100 μM Incubation Duration: 7 days Experimental Results: Anti-proliferation Effects on LNCAP and LNAR cells. In vitro cellular assays for androgen receptor antagonist 1 are conducted in AR-positive prostate cancer cell lines such as LNCaP and VCaP. Cells are treated with the compound at various concentrations, and AR transcriptional activity is measured using luciferase reporter assays. Cell proliferation is measured using MTT or CellTiter-Glo assays. AR protein levels are measured by Western blot to assess degradation when used in PROTACs. These assays characterize the compound’s activity as an AR antagonist and its potential for inducing AR degradation. |
| Animal Protocol |
Animal/Disease Models: Male athymic nude mouse LNCaP CRPC xenograft model [1]
Doses: 100 mg/kg Route of Administration: Orally administered one time/day for 5 weeks. Experimental Results: It has a significant effect in inhibiting tumor growth. At the given dose (100 mg/kg one time/day), tumor growth (90% inhibition) and PSA levels (78%) were almost completely inhibited after 5 weeks, and no weight loss was detected in the animals during treatment. In vivo animal experiments with androgen receptor antagonist 1 are conducted in mouse xenograft models of prostate cancer. Immunodeficient mice are engrafted with AR-positive prostate cancer cells (e.g., LNCaP, VCaP). The compound is administered orally at varying doses. Tumor growth is measured over time, and tumor tissues are harvested for analysis of AR levels and signaling pathways. Pharmacodynamic studies are performed to confirm target engagement and AR degradation. These studies support the development of AR-targeted therapies. |
| ADME/Pharmacokinetics |
Androgen receptor antagonist 1 is an orally available compound with favorable pharmacokinetic properties. It has good oral bioavailability and is suitable for once-daily dosing. The compound’s half-life and tissue distribution have been characterized in preclinical studies. Its pharmacokinetic profile supports its use in vivo for prostate cancer research.
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| Toxicity/Toxicokinetics |
Androgen receptor antagonist 1 has been evaluated for safety in preclinical studies. It is generally well-tolerated at therapeutic doses. Common adverse effects may include those related to androgen deprivation, such as hot flashes, fatigue, and loss of libido. The compound is intended for research use and is not approved for human therapeutic use. Further toxicological studies would be needed for clinical development.
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| References |
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| Additional Infomation |
Androgen receptor antagonist 1 is a potent full AR antagonist used in prostate cancer research. It has an IC50 of 59 nM and is orally available. The compound is used to study hormone signaling, castration-resistant prostate cancer, and endocrine therapy resistance. It can also be used as a ligand for PROTAC AR degraders, inducing AR degradation in LNCaP cells. This dual function makes it a valuable tool for AR-targeted therapy research.
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| Molecular Formula |
C21H25CLN4O3
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| Molecular Weight |
416.901203870773
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| Exact Mass |
416.161
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| CAS # |
1338812-36-4
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| PubChem CID |
56643472
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| Appearance |
White to off-white solid powder
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| LogP |
3.1
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
5
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| Rotatable Bond Count |
6
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| Heavy Atom Count |
29
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| Complexity |
646
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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=NN(CCO)C=1)=O
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| InChi Key |
HJJNHDLYWZTKGQ-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C21H25ClN4O3/c1-20(2)18(25-17(28)14-11-24-26(12-14)7-8-27)21(3,4)19(20)29-15-6-5-13(10-23)16(22)9-15/h5-6,9,11-12,18-19,27H,7-8H2,1-4H3,(H,25,28)
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| Chemical Name |
N-[3-(3-chloro-4-cyanophenoxy)-2,2,4,4-tetramethylcyclobutyl]-1-(2-hydroxyethyl)pyrazole-4-carboxamide
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| Synonyms |
Androgen receptor antagonist 1; Androgen receptor antagonist 1
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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 (~239.87 mM)
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.5 mg/mL (6.00 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (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 25.0 mg/mL clear DMSO stock solution to 900 μL of corn oil and mix evenly. (Please use freshly prepared in vivo formulations for optimal results.) |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 2.3987 mL | 11.9933 mL | 23.9866 mL | |
| 5 mM | 0.4797 mL | 2.3987 mL | 4.7973 mL | |
| 10 mM | 0.2399 mL | 1.1993 mL | 2.3987 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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