| Size | Price | |
|---|---|---|
| 500mg | ||
| 1g | ||
| Other Sizes |
Purity: ≥98%
Fadrozole HCl hydrate (CGS 16949A) is a highly potent and selective nonsteroidal aromatase inhibitor (IC50 of 6.4 nM) with potential antineoplastic activity. Aromatase, a member of the cytochrome P-450 superfamily, is found in many tissues; overexpression has been linked to the development of preneoplastic and neoplastic changes in breast tissue. Check for active clinical trials or closed clinical trials using this agent. Fadrozole specifically inhibits aromatase, blocking the aromatization of androstenedione and testosterone into estrone and estradiol, respectively, the final step in estrogen biosynthesis; the reduction in estrogen levels may inhibit growth in estrogen-dependent cancers.
| Targets |
Aromatase (IC50 = 6 nM)
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|---|---|
| ln Vitro |
To different degrees, the synthesis of other cytochrome P-450-dependent hormones can be inhibited by the use of greater doses of fadrozole hydrochloride hemihydrate [1].
|
| ln Vivo |
When administered orally, fadrozole hydrochloride hemihydrate has an ED50 of 0.03 mg/kg and can prevent aromatase-mediated uterine hypertrophy in immature female rats [1]. In female Sprague-Dawley rats, fadrozole hydrochloride hemihydrate inhibits the growth of benign and malignant spontaneous mammary tumors. 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]. Giving male and female mice fadrozole hydrochloride hemihydrate lowered their parasite burden by 70%. In male mice, this protective effect was linked to the recovery of particular cellular immune responses [3].
|
| 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]
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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]. |
| References |
|
| Additional Infomation |
A selective aromatase inhibitor effective in the treatment of estrogen-dependent disease including breast cancer.
|
| Molecular Formula |
C28H30CL2N6O
|
|---|---|
| Molecular Weight |
537.483403682709
|
| Exact Mass |
536.186
|
| Elemental Analysis |
C, 62.57; H, 5.63; Cl, 13.19; N, 15.64; O, 2.98
|
| CAS # |
176702-70-8
|
| Related CAS # |
Fadrozole hydrochloride;102676-31-3;Fadrozole;102676-47-1;Dexfadrostat;102676-87-9
|
| PubChem CID |
11954367
|
| Appearance |
Typically exists as solid at room temperature
|
| Melting Point |
212 °C
|
| LogP |
6.9
|
| Hydrogen Bond Donor Count |
3
|
| Hydrogen Bond Acceptor Count |
5
|
| Rotatable Bond Count |
2
|
| Heavy Atom Count |
37
|
| Complexity |
311
|
| Defined Atom Stereocenter Count |
0
|
| SMILES |
Cl.Cl.O.N12C=NC=C1CCCC2C1C=CC(C#N)=CC=1.N12C=NC=C1CCCC2C1C=CC(C#N)=CC=1
|
| InChi Key |
RBNOZCGLHXZRLF-UHFFFAOYSA-N
|
| InChi Code |
InChI=1S/2C14H13N3.2ClH.H2O/c2*15-8-11-4-6-12(7-5-11)14-3-1-2-13-9-16-10-17(13)14/h2*4-7,9-10,14H,1-3H22*1H1H2
|
| Chemical Name |
4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile hydrochloride hemihydrate
|
| Synonyms |
CGS 16949A; CGS-16949A ;CGS16949A; Fadrozole hydrochloride hemihydrate; Fadrozole hydrochloride hemihydrate; Fadrozole HCl hydrate; 176702-70-8; UNII-O5207G4XQ9; O5207G4XQ9; Fadrozole hydrochloride hydrate; 176702-70-8 (HCl hydrate); 4-(5,6,7,8-tetrahydroimidazo[1,5-a]pyridin-5-yl)benzonitrile hydrochloride hemihydrate;
|
| 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)
|
| 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 | 1.8605 mL | 9.3027 mL | 18.6053 mL | |
| 5 mM | 0.3721 mL | 1.8605 mL | 3.7211 mL | |
| 10 mM | 0.1861 mL | 0.9303 mL | 1.8605 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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