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| Targets |
5 alpha-reductase
Dihydro Dutasteride targets 5α-reductase isozymes. Dutasteride is a potent inhibitor of both 5α-reductase isozymes. By inhibiting these enzymes, it blocks the conversion of testosterone to dihydrotestosterone (DHT), reducing androgen action in target tissues. |
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| ln Vitro |
Dutasteride inhibited (3)H-T conversion to (3)H-DHT and, as anticipated, inhibited T-induced secretion of PSA and proliferation. However the drug also inhibited DHT-induced PSA secretion and cell proliferation (IC(50) approximately 1 microM). Finasteride also inhibited DHT action but was less potent than dutasteride. Dutasteride competed for binding the LNCaP cell AR with an IC(50) approximately 1.5 microM. High concentrations of dutasteride (10-50 microM), but not finasteride, in steroid-free medium, resulted in enhanced cell death, possibly by apoptosis. This was accompanied by loss of AR protein and decreased AR ligand-binding activity. Occupation of AR by R1881 partly protected against cell death and loss of AR protein. PC-3 prostate cancer cells, which do not contain AR, also were killed by high concentrations of dutasteride, as well as by 50 microM finasteride. Conclusions: Dutasteride exhibited some inhibitory actions in LNCaP cells possibly related to 5alphaR inhibition but also had antiandrogenic effects at relatively low concentrations and cell death-promoting effects at higher concentrations. Finasteride also was antiandrogenic, but less than dutasteride. The antiandrogenic effects may be mediated by the mutant LNCaP cell AR. Promotion of cell death by dutasteride can be blocked, but only in part, by androgens[1].
Dihydro Dutasteride effectively inhibits 5α-reductase isozymes. As a metabolite and impurity of Dutasteride, it is expected to retain 5α-reductase inhibitory activity. Its activity makes it a valuable tool for studying androgen metabolism and 5α-reductase function. |
| ln Vivo |
Short-term Dutasteride treatments with concentrations of 1 and 10 mg/kg significantly increase the total PSMA protein expression in a mouse LNCaP xenograft model. PSMA fluorescence intensity increases significantly even using lower daily concentrations of 0.1 mg/kg Dutasteride. Further investigations are needed to elucidate the impact of Dutasteride treatment on PSMA expression in patients. Cancer Rep (Hoboken). 2021 Dec;4(6):e1418.
Dihydro Dutasteride is a metabolite formed following Dutasteride administration. Dutasteride is approved for the treatment of benign prostatic hyperplasia. The metabolite contributes to the overall pharmacokinetic profile of the parent drug. Its role in vivo is primarily understood through pharmacokinetic studies. |
| Enzyme Assay |
In vitro enzyme assays for Dihydro Dutasteride involve measuring its inhibition of 5α-reductase activity. The enzyme is incubated with increasing concentrations of the compound and testosterone as substrate. The conversion of testosterone to dihydrotestosterone is measured by HPLC or radioimmunoassay. IC50 values are calculated from dose-response curves.
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| Cell Assay |
Reduction of T to DHT by 5alphaR in the prostate enhances androgenic activity for most targets. Inhibition of 5alphaR activity with finasteride attenuates androgen action in men and animal models. The objective of this study was to compare and contrast the effects of a potent new 5alphaR inhibitor, dutasteride, with finasteride in the LNCaP prostate cancer cell line. Methods: LNCaP cells were incubated for varying times with T or DHT in steroid-free medium in the absence or presence of increasing doses of dutasteride or finasteride and the effects on 5alphaR activity, PSA accumulation in the medium, and on cell proliferation were determined. Drug effects on apoptosis were investigated using Annexin V staining and a cell death ELISA assay. Effects of the drugs on AR ligand-binding activity and on AR protein levels were determined[1].
For in vitro cell-based assays, cells expressing 5α-reductase are cultured and treated with Dihydro Dutasteride at various concentrations. The conversion of testosterone to DHT is measured in cell lysates or media. Cell viability is assessed by standard assays. The compound's effects on androgen receptor signaling can be assessed in prostate cancer cell lines. |
| Animal Protocol |
Four groups of mice bearing LNCaP xenografts were treated for 14 days with daily intraperitoneal injections of either vehicle control or different concentrations of Dutasteride (0.1, 1, 10 mg/kg). Total expression of PSMA, androgen receptor (AR), and caspase-3 protein was analyzed using immunoblotting (WES). In addition, PSMA, cleaved caspase-3 and Ki-67 expression was assessed and quantified by immunohistochemistry. Tumor size was measured by caliper on day 7 and 14, tumor weight was assessed following tissue harvesting. The mean PSMA protein expression in mice increased significantly after treatment with 1 mg/kg (10-fold) or 10 mg/kg (sixfold) of Dutasteride compared to vehicle control. The mean fluorescence intensity significantly increased by daily injections of 0.1 mg/kg Dutasteride (1.6-fold) as well as 1 and 10 mg/kg Dutasteride (twofold). While the reduction in tumor volume following treatment with high concentrations of 10 mg/kg Dutasteride was nonsignificant, no changes in AR, caspase-3, cleaved caspase-3, and Ki-67 expression were observed.Cancer Rep (Hoboken)
. 2021 Dec;4(6):e1418.
In vivo animal studies with Dihydro Dutasteride are primarily pharmacokinetic. The compound is administered to rodents, and blood samples are collected at predetermined time points. Plasma concentrations are analyzed by LC-MS/MS. Pharmacodynamic effects can be evaluated in models of benign prostatic hyperplasia. |
| ADME/Pharmacokinetics |
Dihydro Dutasteride (CAS: 164656-22-8) has a molecular weight of 530.55 g/mol and a molecular formula of C27H32F6N2O2. Appearance: solid powder. Purity: ≥95%. Storage: -20°C. The compound is a metabolite and impurity of Dutasteride.
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| Toxicity/Toxicokinetics |
Dihydro Dutasteride is a research compound and is not approved for human therapeutic use as a standalone drug. As a metabolite of an approved drug, it shares the toxicity profile of Dutasteride, which is generally well-tolerated. Standard laboratory safety precautions should be followed when handling the compound.
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| References |
[1]. Dutasteride, the dual 5alpha-reductase inhibitor, inhibits androgen action and promotes cell death in the LNCaP prostate cancer cell line. Prostate. 2004 Feb 1;58(2):130-44.
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| Additional Infomation |
Previous in vitro studies have shown that dutasteride can increase the expression of prostate-specific membrane antigen (PSMA) in prostate cancer cells. This 5α-reductase inhibitor is commonly used to treat symptomatic benign prostatic hyperplasia. Regulation of PSMA expression may affect PSMA-based imaging and treatment of prostate cancer. Objective: This study aimed to further analyze the concentration-dependent effect of dutasteride on PSMA expression in a mouse xenograft model. Cancer Rep (Hoboken). 2021 Dec;4(6):e1418.
Dihydro Dutasteride is a metabolite and impurity of Dutasteride, a potent 5α-reductase inhibitor approved for benign prostatic hyperplasia. It effectively inhibits 5α-reductase isozymes. It is not FDA-approved as a standalone drug and is intended for research use only. |
| Molecular Formula |
C27H32F6N2O2
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|---|---|
| Molecular Weight |
530.54600
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| Exact Mass |
530.237
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| Elemental Analysis |
C, 61.12; H, 6.08; F, 21.49; N, 5.28; O, 6.03
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| CAS # |
164656-22-8
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| PubChem CID |
15871205
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| Appearance |
Typically exists as solid at room temperature
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| LogP |
7.201
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| Hydrogen Bond Donor Count |
2
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| Hydrogen Bond Acceptor Count |
8
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| Rotatable Bond Count |
2
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| Heavy Atom Count |
37
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| Complexity |
922
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| Defined Atom Stereocenter Count |
7
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| SMILES |
C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2C(=O)Nc4cc(ccc4C(F)(F)F)C(F)(F)F)CC[C@@H]5[C@@]3(CCC(=O)N5)C
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| InChi Key |
AIUHDIPAGREENV-QWBYCMEYSA-N
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| InChi Code |
InChI=1S/C27H32F6N2O2/c1-24-11-9-17-15(4-8-21-25(17,2)12-10-22(36)35-21)16(24)6-7-19(24)23(37)34-20-13-14(26(28,29)30)3-5-18(20)27(31,32)33/h3,5,13,15-17,19,21H,4,6-12H2,1-2H3,(H,34,37)(H,35,36)/t15-,16-,17-,19+,21+,24-,25+/m0/s1
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| Chemical Name |
(1S,3aS,3bS,5aR,9aR,9bS,11aS)-N-[2,5-bis(trifluoromethyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,8,9,9b,10,11-tetradecahydroindeno[5,4-f]quinoline-1-carboxamide
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| Synonyms |
Dihydro Dutasteride; 164656-22-8; Dihydrodutasteride; 1,2-Dihydrodutasteride; Y7B42KG7F8; GI201448X; (1S,3aS,3bS,5aR,9aR,9bS,11aS)-N-[2,5-bis(trifluoromethyl)phenyl]-9a,11a-dimethyl-7-oxo-1,2,3,3a,3b,4,5,5a,6,8,9,9b,10,11-tetradecahydroindeno[5,4-f]quinoline-1-carboxamide; 1H-Indeno(5,4-F)quinoline-7-carboxamide, N-(2,5-bis(trifluoromethyl)phenyl)hexadecahydro-4a,6a-dimethyl-2-oxo-, (4aR,4bS,6aS,7S,9aS,9bS,11aR)-;
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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 | 1.8848 mL | 9.4242 mL | 18.8484 mL | |
| 5 mM | 0.3770 mL | 1.8848 mL | 3.7697 mL | |
| 10 mM | 0.1885 mL | 0.9424 mL | 1.8848 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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