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Chemical Structure| 102676-47-1 Chemical Structure| 102676-47-1

Structure of Fadrozole
CAS No.: 102676-47-1

Chemical Structure| 102676-47-1

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Fadrozole is a selective aromatase inhibitor that has been introduced in Japan for the treatment of breast cancer.

Synonyms: CGS 16949A free base; (Rac)-FAD286; CGS16949A

4.5 *For Research Use Only !

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Product Citations

Product Citations

Hideaki Ishii ; Yuhiro Ishikawa ; Fumiaki Mizobe ; Motoi Nomura ; Takashi Yamanaka ; Sohei Tanabe , et al.

Abstract: Rationale Osilodrostat is an inhibitor of 11-beta-hydroxylase (CYP11B) and is used for the treatment of Cushing's disease but also categorized as an anabolic agent. The use of osilodrostat is prohibited in horseracing and equestrian sports. To the best of our knowledge, this is the first metabolic study of osilodrostat in equine plasma. Methods Potential metabolites of osilodrostat were identified by differential analysis using data acquired from pre- and post-administration plasma samples after protein precipitation with liquid chromatography electrospray ionization high-resolution mass spectrometry (LC/ESI–HRMS). [Correction added on 27 January 2023, after first online publication: In the preceding sentence, “C–HRMS” was changed to “LC/ESI–HRMS” in this version.] For quantification of osilodrostat, a strong cation exchange solid-phase extraction was employed, and the extracts were analyzed using LC/ESI–triple quadrupole tandem mass spectrometry (LC/ESI–QqQ-MS/MS) to establish its elimination profile. Such extracts were further analyzed using LC/ESI–HRMS to investigate the detectability of osilodrostat and its identified mono-hydroxylated metabolite over a 2-week sampling period. Results Mono-hydroxylated osilodrostat was identified based on the differential analysis and mass spectrometric interpretations, and it was found to be the most abundant metabolite in plasma. Elimination profile of osilodrostat in plasma was successfully established over the 24-h post-administration period. Both osilodrostat and its mono-hydroxylated metabolite were detected up to the last sampling point at 2 weeks using HRMS, and osilodrostat could be confirmed up to 8-day post-administration with its reference material using HRMS as well. Conclusions For doping control, screening of both the parent drug osilodrostat and its mono-hydroxylated metabolite in equine plasma would be recommended due to their extended detection windows of up to 2 weeks. Given the availability of reference material for potential confirmation in forensic samples, osilodrostat is considered the most appropriate monitoring target.

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Product Details of Fadrozole

CAS No. :102676-47-1
Formula : C14H13N3
M.W : 223.27
SMILES Code : N#CC1=CC=C(C2CCCC3=CN=CN23)C=C1
Synonyms :
CGS 16949A free base; (Rac)-FAD286; CGS16949A
MDL No. :MFCD02313480

Safety of Fadrozole

GHS Pictogram:
Signal Word:Danger
Hazard Statements:H301-H361
Precautionary Statements:P281-P301+P310
Class:6.1
UN#:2811
Packing Group:

Isoform Comparison

Biological Activity

In Vivo:

Species
Animal Model
Administration Dosage Frequency Description References
Male rats Gonadectomized rat model Bilateral infusion into the dentate gyrus of the hippocampus 1.0μg Continuous infusion, 6μL/day To evaluate the inhibitory effect of fadrozole on testosterone's antidepressant- and anxiolytic-like behaviors. Results showed that fadrozole blocked the anxiolytic and antidepressant-like effects of testosterone. PMC4501899
Fathead minnow (Pimephales promelas) Reproductively mature adult fathead minnows Waterborne exposure 3 or 30 µg 8-day exposure followed by an 8-day recovery period To investigate the molecular and biochemical responses of female fathead minnows to the aromatase inhibitor Fadrozole, including direct effects, compensation, and/or recovery. Results showed significant reductions in plasma 17β-estradiol (E2) and vitellogenin (Vtg) concentrations during exposure, with recovery observed during the post-exposure period. PMC2679608
Chicken embryos Chicken embryo sex reversal model In ovo injection 1 mg,100μL Single injection at E3.5, or double injections at E3.5 and E6.5 To study the effect of Fadrozole on sex reversal in chicken embryos, it was found that Fadrozole treatment caused female embryos to develop into ovotestis containing PAX2-positive undifferentiated supporting cells. PMC9684329
Chickens Sex-reversed chicken model Injected into the air sac 1.0 mg Single injection Fadrozole significantly affected the transcriptional activities of several genes related to sex determination and differentiation, such as DMRT1, SOX9, FOXL2, and CYP19A1, and regulated the expression of a set of gonadal development-related genes by modulating nearby open chromatin regions in sex-reversed chicken embryos. PMC9827654

Clinical Trial:

NCT Number Conditions Phases Recruitment Completion Date Locations
NCT00247663 Postmenopausal Women With Adva... More >>nced Breast Cancer Less << Phase 2 Completed - Japan ... More >> Novartis Investigative Site Kashiwa, Chiba, Japan, 277-8577 Novartis Investigative Site Amagasaki, Hyogo, Japan, 660-8511 Novartis Investigative Site Hamamatsu, Shizuoka, Japan, 430-8558 Novartis Investigative Site Chuo-Ku, Tokyo, Japan, 104-0045 Novartis Investigative Site Cyuo-ku, Tokyo, Japan, 104-8560 Novartis Investigative Site Shinjuku-ku, Tokyo, Japan, 160-8582 Novartis Investigative Site Fukuoka, Japan, 811-4395 Novartis Investigative Site Kumamoto, Japan, 862-0909 Novartis Investigative Site Nigata, Japan, 951-8566 Novartis Investigative Site Saitama, Japan, 338-8553 Less <<
NCT03279289 Metastatic Colorectal Cancer Phase 2 Recruiting July 2021 Spain ... More >> Spanish Cooperative Group for Digestive Tumour Therapy (TTD) Recruiting Madrid, Spain, 28046 Contact: Inmaculada Ruiz de Mena, PhD    0034 91 378 82 75    ttd@ttdgroup.org Less <<

Protocol

Bio Calculators
Preparing Stock Solutions 1mg 5mg 10mg

1 mM

5 mM

10 mM

4.48mL

0.90mL

0.45mL

22.39mL

4.48mL

2.24mL

44.79mL

8.96mL

4.48mL

Dissolving Methods
Please choose the appropriate dissolution scheme according to your animal administration guide.For the following dissolution schemes, clear stock solution should be prepared according to in vitro experiments, and then cosolvent should be added in turn:

in order to ensure the reliability of the experimental results, the clarified stock solution can be properly preserved according to the storage conditions; The working fluid for in vivo experiment is recommended to be prepared now and used on the same day;

The percentage shown in front of the following solvent refers to the volume ratio of the solvent in the final solution; If precipitation or precipitation occurs in the preparation process, it can be assisted by heating and/or ultrasound.
Protocol 1
Protocol 2

References

 

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