| Size | Price | Stock | Qty |
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| 10mg |
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| 25mg |
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| 50mg |
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| 100mg |
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| 250mg | |||
| Other Sizes |
Purity: ≥98%
| Targets |
Aromatase (IC50 = 6 nM)
Fadrozole HCl targets the aromatase enzyme (CYP19A1), which catalyzes the conversion of androgens to estrogens. By selectively inhibiting aromatase, fadrozole HCl reduces estrogen biosynthesis in peripheral tissues and tumors. This mechanism deprives estrogen-dependent breast cancer cells of the hormonal stimulation required for growth. The hydrochloride salt form provides improved aqueous solubility for research applications. |
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| ln Vitro |
With an IC50 of 6.4 nM, fadrozole hydroHClide is a very effective and specific nonsteroidal aromatase inhibitor. With an IC50 of 0.03 μM, fadrozole hydrochloride suppresses the synthesis of estrogen in hamster ovarian slices. The IC50 value for the inhibition of progesterone production is 120 μM. To different degrees, the manufacture of additional cytochrome P-450-dependent hormones can be inhibited by high doses of fadrozole hydrochloride [1].
In vitro, fadrozole HCl potently inhibits aromatase activity in a concentration-dependent manner. The compound shows high selectivity for aromatase over other cytochrome P450 enzymes. In cell-based assays, fadrozole HCl reduces estradiol production in aromatase-expressing cells and inhibits the proliferation of estrogen-dependent breast cancer cell lines. The compound's IC₅₀ for aromatase inhibition has been characterized in various enzyme assays. |
| ln Vivo |
Orally given benzodiazepine hydrochloride has an ED50 of 0.03 mg/kg and can suppress aromatase-mediated uterine hypertrophy in immature female rats. Oral aminoglutethimide dosing produced the same result in the same model, with an ED50 of 30 mg/kg [1]. In female Sprague-Dawley rats, fadrozole hydrochloride inhibits the growth of spontaneous mammary tumors, both benign and malignant. Additionally, it lowers the incidence of spontaneous hepatocellular tumors in both male and female rats and inhibits the spontaneous formation of distal pituitary adenomas in female rats [2]. The parasite burden in male and female mice treated with fadrozole hydrochloride was reduced by 70%. In male mice, this protection was linked to the recovery of particular cellular immune responses. Interleukin-6 (IL-6) expression in the testes of infected male mice increased tenfold, while serum levels and splenocyte synthesis of the substance increased by 80%. These levels recover to baseline amounts following treatment with fadrozole hydrochloride [3].
In vivo, fadrozole HCl has demonstrated efficacy in reducing circulating estrogen levels and inhibiting the growth of estrogen-dependent tumors in animal models. The compound's oral bioavailability supports convenient dosing. Fadrozole HCl has been evaluated in clinical studies for the treatment of advanced breast cancer in postmenopausal women. |
| Enzyme Assay |
For in vitro tests, culture grade Fadrozole was dissolved in cRPMI to the desired stock concentration, and sterilised by passage through a 0.2-mm Millipore filter. Experimental design was as follows: using a 24-well culture plate, six wells were used as untreated controls, six wells were supplemented with the vehicle in which Fadrozole was diluted, six wells were treated with different concentrations of Fadrozole. Concentrations of Fadrozole were randomised across the plates. Fadrozole was prepared to a final volume of 100 μl and added to 2 ml of medium in each well. Control cysts were treated with the solvent in which Fadrozole was diluted such that a constant volume of solvent (100 μl) was added to each well. Reproduction was measured as the number of buds that each cyst produced in response to treatment and were counted directly under a light inverted microscope. Morbidity of cysts was recognised by progressive internal disorganisation, development of lucent areas in the cytoplasm, and progressive loss of motility. Dead cysts had an opaque appearance with lucent areas in the tegmental cytoplasm and characteristic swelling. Viability was based upon granularity, bodily contortions, and methylene blue uptake. Unstained cysts were considered dead when they lacked motility and/or were characteristically granular. All viability observations were determined microscopically, and cysts were considered dead based on complete loss of motility of the anterior and posterior regions, and internal loss of movement for food intake. These observations were done under an inverted microscope using 10× and 100× magnification.[3]
Non-cellular enzyme assays for fadrozole HCl involve assessing its inhibition of aromatase using human placental microsomes or recombinant CYP19A1 enzyme. The enzyme is incubated with [³H]-androstenedione and NADPH in the presence of varying concentrations of fadrozole HCl. The conversion to [³H]-estrone is measured by scintillation counting after extraction. IC₅₀ values for aromatase inhibition are determined from dose-response curves. |
| Cell Assay |
In vitro cellular assays for fadrozole HCl involve treating aromatase-expressing cell lines (e.g., JEG-3 choriocarcinoma cells or MCF-7 breast cancer cells) with the compound. The inhibition of estradiol production is measured by ELISA or radioimmunoassay in the culture medium. Cell proliferation assays are used to assess the functional consequences of estrogen depletion on estrogen-dependent cell growth. Cells are treated with varying concentrations of fadrozole HCl for 48-72 hours.
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| Animal Protocol |
Fadrozole was administered in the form of sub-dermal long-term release pellets (20 mg/wt kg, in three-week-release pellets), starting 1 week prior to the infection, using a 10-gauge needle Trochar. Three pellets were administrated during the study. Placebo pellets were administered to another group of infected mice, in the same fashion as the inhibitor. After 1 week, mice were infected as described above and killed 8 weeks later.[3]
Rats are treated with daily dosing with fadrozole hydrochloride (CGS 16949A) in purified water by gavage for 2 years. There are 60 rats in each of four groups given 0, 0.05, 0.25 or 1.25 mg/kg daily. Control rats receive only water. Clinical signs are recorded weekly and the animals are examine for palpable masses every 4 weeks for the first 9 months, then every 2 weeks for the remainder of the study[2]. Mice: Fadrozole is administered in the form of sub-dermal long-term release pellets (20 mg/wt kg, in three-week-release pellets), starting 1 week prior to the infection, using a 10-gauge needle. Three pellets are administrated during the study. Placebo pellets are administered to another group of infected mice, in the same fashion as the inhibitor. After 1 week, mice are infected and killed 8 weeks later[3]. In vivo animal experiments with fadrozole HCl are conducted in rodent models of estrogen-dependent tumors. Ovariectomized or intact female rats with xenografted MCF-7 tumors are treated with fadrozole HCl via oral administration. Tumor growth inhibition is monitored by caliper measurements. Serum estradiol levels are measured by ELISA or radioimmunoassay. Uterine weight is assessed as a pharmacodynamic marker. |
| ADME/Pharmacokinetics |
Fadrozole HCl has a molecular weight of 268.70 and a molecular formula of C₁₃H₁₄ClN₃. It is a solid at room temperature with a purity of ≥98%. The compound is soluble in water and other polar solvents, as well as DMSO. It is typically stored at -20°C, protected from light and moisture. The hydrochloride salt provides improved aqueous solubility compared to the free base.
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| Toxicity/Toxicokinetics |
Fadrozole HCl is a research compound for laboratory use only and is not approved for human therapeutic use. In preclinical studies, it has been generally well-tolerated at therapeutic doses. Standard laboratory safety precautions should be followed when handling the compound. It may cause skin, eye, and respiratory irritation. Appropriate personal protective equipment should be used.
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| References |
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| Additional Infomation |
Fadrozole hydrochloride is an imidazopyridine compound. It is the hydrochloride salt of Fadrozole, a nonsteroidal aromatase inhibitor with potential antitumor activity. Fadrozole specifically inhibits aromatase, blocking the aromatization of androstenedione and testosterone into estrone and estradiol, respectively, the final step in estrogen biosynthesis; reduced estrogen levels may inhibit the growth of estrogen-dependent cancers. Aromatase is a member of the cytochrome P-450 superfamily and is present in various tissues; its overexpression is associated with the development and progression of precancerous lesions and tumors in breast tissue. Selective aromatase inhibitors can effectively treat estrogen-dependent diseases, including breast cancer.
Fadrozole HCl (CGS-16949A; CAS 102676-31-3) is the hydrochloride salt form of fadrozole, a potent, nonsteroidal, and selective aromatase inhibitor. It was developed for the treatment of estrogen-dependent breast cancer. The hydrochloride salt provides improved aqueous solubility for research applications. The compound is available from various commercial suppliers. |
| Molecular Formula |
C14H14CLN3
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|---|---|
| Molecular Weight |
259.73406
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| Exact Mass |
259.088
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| Elemental Analysis |
C, 64.74; H, 5.43; Cl, 13.65; N, 16.18
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| CAS # |
102676-31-3
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| Related CAS # |
Fadrozole;102676-47-1;Dexfadrostat;102676-87-9;Fadrozole hydrochloride hemihydrate;176702-70-8;
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| PubChem CID |
59694
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| Appearance |
White to off-white solid powder
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| Boiling Point |
481.7ºC at 760mmHg
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| Flash Point |
245.1ºC
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| Vapour Pressure |
1.95E-09mmHg at 25°C
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| LogP |
3.482
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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 |
1
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| Heavy Atom Count |
18
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| Complexity |
311
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| Defined Atom Stereocenter Count |
0
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| InChi Key |
UKCVAQGKEOJTSR-UHFFFAOYSA-N
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| InChi Code |
InChI=1S/C14H13N3.ClH/c15-8-11-4-6-12(7-5-11)14-3-1-2-13-9-16-10-17(13)14/h4-7,9-10,14H,1-3H21H
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| Chemical Name |
Benzonitrile, 4-(5,6,7,8-tetrahydroimidazo(1,5-a)pyridin-5-yl)-, monohydrochloride
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| Synonyms |
Fadrozole hydrochloride; CGS 16949A; CGS-16949A; FADROZOLE HYDROCHLORIDE; 102676-31-3; Afema; Fadrozole HCl; CGS 16949A; 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile hydrochloride; Fadrozole.HCl; Benzonitrile, 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)-, hydrochloride (1:1); CGS16949A
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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: Please store this product in a sealed and protected environment, 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) |
H2O : ~100 mg/mL (~385.02 mM)
DMSO : ~100 mg/mL (~385.02 mM) |
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| Solubility (In Vivo) |
Solubility in Formulation 1: ≥ 2.08 mg/mL (8.01 mM) (saturation unknown) in 10% DMSO + 40% PEG300 + 5% Tween80 + 45% Saline (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 20.8 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: ≥ 2.08 mg/mL (8.01 mM) (saturation unknown) in 10% DMSO + 90% (20% SBE-β-CD in Saline) (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 20.8 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: ≥ 2.08 mg/mL (8.01 mM) (saturation unknown) in 10% DMSO + 90% Corn Oil (add these co-solvents sequentially from left to right, and one by one), clear solution. Solubility in Formulation 4: 100 mg/mL (385.02 mM) in PBS (add these co-solvents sequentially from left to right, and one by one), clear solution; with ultrasonication. |
| Preparing Stock Solutions | 1 mg | 5 mg | 10 mg | |
| 1 mM | 3.8502 mL | 19.2508 mL | 38.5015 mL | |
| 5 mM | 0.7700 mL | 3.8502 mL | 7.7003 mL | |
| 10 mM | 0.3850 mL | 1.9251 mL | 3.8502 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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