| Size | Price | Stock | Qty |
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| 5mg |
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| 10mg |
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| Other Sizes |
| Targets |
Androgen receptor (AR) and 5alpha-reductase. Cl-4AS-1 is a steroidal androgen receptor agonist with an IC50 of 12 nM. It binds to AR with high affinity, transactivates the mouse mammary tumor virus (MMTV) promoter, and represses MMP1 promoter activity. The compound also inhibits 5alpha-reductase type I (IC50 = 6 nM) and type II (IC50 = 10 nM), thereby blocking the conversion of testosterone to the more potent androgen DHT. This dual activity profile gives it unique tissue-selective properties, acting as an AR full agonist in some tissues while limiting androgenic effects in others.
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| ln Vitro |
In 22Rv1 human prostate cancer cells, Cl-4AS-1 suppresses MMP-1 promoter activity [1]. At an average maximum activity of 35.3%, Cl-4AS-1 (10 μM) efficiently stimulates AR N/C interaction[1].
In cell-free assays, Cl-4AS-1 binds directly to the androgen receptor with an IC50 of 12 nM. AR binding affinity is measured by competition binding assays using radiolabeled [3H]-DHT or [3H]-R1881 and purified AR protein or AR-containing cell lysates. The compound also inhibits 5alpha-reductase activity in cell-free assays using rat prostate or liver microsomal fractions as an enzyme source. Inhibition of 5alpha-reductase type I (IC50 = 6 nM) and type II (IC50 = 10 nM) is measured by quantifying the conversion of [14C]-testosterone to [14C]-DHT. |
| ln Vivo |
Cl-4AS-1 does not significantly lower prostate weight in intact animals, but produces a large rise in ventral prostate weight in castrated rats [1].
In cell-based assays, Cl-4AS-1 (10 uM) efficiently stimulates AR N/C (N-terminal/carboxyl-terminal) interaction, with an average maximal activity of 35.3%. The compound transactivates AR-dependent reporter genes, including the MMTV-luciferase reporter in AR-positive cell lines. In 22Rv1 human prostate cancer cells, Cl-4AS-1 suppresses MMP-1 promoter activity. It also represses the expression of androgen-responsive genes in a tissue-specific manner. Cl-4AS-1 does not significantly stimulate proliferation of LNCaP cells under standard culture conditions. The compound's ability to both activate AR and inhibit 5alpha-reductase gives it a unique pharmacological profile. |
| Enzyme Assay |
Androgen receptor binding assays are performed in a competition format. AR protein (e.g., from LNCaP cell lysates or recombinant AR-LBD) is incubated with 0.5-1 nM [3H]-R1881 (a synthetic androgen) and increasing concentrations of unlabeled Cl-4AS-1 (0.1-1000 nM) in binding buffer for 16-24 hours at 4degC. Bound and free radioligand are separated by charcoal-dextran precipitation or filtration. Specific binding is calculated, and IC50 values are determined from competition curves. Ki values are calculated using the Cheng-Prusoff equation. For 5alpha-reductase assays, rat prostate microsomes are incubated with [14C]-testosterone (0.5-5 uM), NADPH (1 mM), and Cl-4AS-1 (0-1000 nM) for 30-60 minutes at 37degC. Steroids are extracted with ethyl acetate, separated by thin-layer chromatography (TLC), and quantified by autoradiography or phosphorimaging. IC50 values for inhibition of DHT formation are calculated.
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| Cell Assay |
Reporter gene assays are performed in AR-positive cell lines (e.g., LNCaP, MDA-MB-453, or AR-negative cells transiently transfected with AR expression vector and an ARE-luciferase reporter). Cells are seeded in 96-well plates and cultured in charcoal-stripped serum-containing medium for 24-48 hours. Cells are then treated with Cl-4AS-1 (0.1-1000 nM) in the presence or absence of DHT or R1881 for 16-24 hours. Luciferase activity is measured using a luciferase assay reagent, and relative light units are normalized to protein content or a constitutively expressed reporter. EC50 values for transcriptional activation are calculated. For AR N/C interaction assays, cells expressing AR fragments fused to complementary fragments of a split luciferase or split GFP are treated with Cl-4AS-1 (0.1-100 uM) and complementation measured by luminescence or fluorescence.
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| Animal Protocol |
Animal/Disease Models: ORX rat[1]
Doses: 10 mg/kg Route of Administration: Is; 7-day Experimental Results: Effect of Cl-4AS-1 on prostate and seminal vesicle growth. In vivo studies of Cl-4AS-1 have been conducted in ovariectomized (OVX) rats and castrated (ORX) rats. In OVX rats, Cl-4AS-1 mimics DHT action, promoting the accrual of bone and muscle mass while having reduced effects on reproductive tissues and sebaceous glands. This tissue-selective profile indicates that Cl-4AS-1 has anabolic effects with less androgenic side effects. In castrated rats, Cl-4AS-1 produces a large rise in ventral prostate weight, indicating AR agonism. However, in intact animals, Cl-4AS-1 does not significantly lower prostate weight, suggesting that it acts differently in the presence of endogenous androgens. The compound's dual AR agonist/5alpha-reductase inhibitor activity gives it a unique in vivo profile. Typical doses range from 0.1-10 mg/kg administered subcutaneously or orally. |
| ADME/Pharmacokinetics |
Formal PK studies for Cl-4AS-1 have not been fully reported. As a steroidal compound, it is expected to have moderate oral bioavailability, significant plasma protein binding, and distribution to steroid-sensitive tissues. The compound is soluble in DMSO and ethanol. In vivo formulations typically use DMSO or ethanol-based vehicles diluted in saline or oil for injection. The presence of both AR agonist and 5alpha-reductase inhibitor activities may affect the disposition and metabolism of endogenous androgens. Detailed PK parameters such as half-life, clearance, and volume of distribution have not been published.
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| Toxicity/Toxicokinetics |
Preclinical toxicology data for Cl-4AS-1 are limited. The compound is used as a research tool at relatively low doses and is generally considered to have acceptable tolerability in animal studies. Adverse effects are expected to be related to its androgenic and anti-androgenic activities. Traditional anabolic steroids are associated with hepatotoxicity, cardiovascular effects, and hormonal imbalances. Cl-4AS-1 was designed to minimize androgenic side effects while maintaining anabolic activity. At standard research doses, no significant toxicity has been reported. Standard laboratory safety practices should be followed when handling this compound.
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| References |
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| Additional Infomation |
Cl-4AS-1 is a research compound used to study selective androgen receptor modulation (SARM). It was originally developed as part of efforts to identify anabolic agents with reduced effects on reproductive tissues and sebaceous glands. The compound is also known by its full chemical name and is sometimes referred to as 4-aza-3-oxo-4,7beta-dimethyl-17beta-(N-2-chlorophenylcarbamoyl)estr-5-ene. Cl-4AS-1 is a structural analog of finasteride, a 5alpha-reductase inhibitor. The TFM derivative (TFM-4AS-1) is a partial agonist SARM. Cl-4AS-1 is not approved for human use. The compound has potential therapeutic applications in conditions like muscle wasting or osteoporosis. It is also known to inhibit 5alpha-reductase, which may have applications in benign prostatic hyperplasia and androgenetic alopecia.
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| Molecular Formula |
C26H33CLN2O2
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|---|---|
| Molecular Weight |
441.005426168442
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| Exact Mass |
440.223
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| CAS # |
188589-66-4
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| PubChem CID |
9932961
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| Appearance |
White to off-white solid powder
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| LogP |
5.545
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| Hydrogen Bond Donor Count |
1
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| Hydrogen Bond Acceptor Count |
2
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
31
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| Complexity |
783
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| Defined Atom Stereocenter Count |
7
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| SMILES |
ClC1=CC=CC=C1NC(C1CCC2C3CCC4N(C(C=CC4(C)C3CCC12C)=O)C)=O
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| InChi Key |
CTVXDPDUOKQBKZ-GFNRTWGOSA-N
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| InChi Code |
InChI=1S/C26H33ClN2O2/c1-25-14-12-18-16(8-11-22-26(18,2)15-13-23(30)29(22)3)17(25)9-10-19(25)24(31)28-21-7-5-4-6-20(21)27/h4-7,13,15-19,22H,8-12,14H2,1-3H3,(H,28,31)/t16-,17-,18-,19+,22+,25-,26+/m0/s1
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| Chemical Name |
(1S,3aS,3bS,5aR,9aR,9bS,11aS)-N-(2-chlorophenyl)-6,9a,11a-trimethyl-7-oxo-2,3,3a,3b,4,5,5a,9b,10,11-decahydro-1H-indeno[5,4-f]quinoline-1-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) |
May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples
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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 | 2.2675 mL | 11.3376 mL | 22.6752 mL | |
| 5 mM | 0.4535 mL | 2.2675 mL | 4.5350 mL | |
| 10 mM | 0.2268 mL | 1.1338 mL | 2.2675 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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