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fadrozole   Click here for help

GtoPdb Ligand ID: 8311

Synonyms: Afema® | CGS 16949 A [1] | CGS-16949A | FAD 286 | FAD-286
Approved drug
fadrozole is an approved drug (Japan only)
Compound class: Synthetic organic
Comment: Fadrozole was designed and reported as a selective aromatase (CYP19A1) inhibitor having only weak effects on aldosterone and cortisol production [1]. More recent evidence suggests that fadrozole is in fact a potent inhibitor of the cytochrome P450 enzymes, CYP11B1 (11-beta-hydroxylase) and CYP11B2 (aldosterone synthase) responsible for cortisol and aldosterone synthesis respectively [2]. Fadrozole is a racemic mixture. Evidence suggests that the (5S) enantiomer (dexfadrostat) preferentially inhibits CYP11B1, whilst the (5R) enantiomer is more selective for CYP11B2 [3].
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species

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2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/). All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 2
Hydrogen bond donors 0
Rotatable bonds 1
Topological polar surface area 41.61
Molecular weight 223.11
XLogP 3.1
No. Lipinski's rules broken 0

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)

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Canonical SMILES N#Cc1ccc(cc1)C1CCCc2n1cnc2
Isomeric SMILES N#Cc1ccc(cc1)C1CCCc2n1cnc2
InChI InChI=1S/C14H13N3/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,1-3H2
InChI Key CLPFFLWZZBQMAO-UHFFFAOYSA-N

Generated using the Chemistry Development Kit (CDK) (Willighagen EL et al. Journal of Cheminformatics vol. 9:33. 2017, doi:10.1186/s13321-017-0220-4; https://cdk.github.io/)
References
1. Browne LJ, Gude C, Rodriguez H, Steele RE, Bhatnager A. (1991)
Fadrozole hydrochloride: a potent, selective, nonsteroidal inhibitor of aromatase for the treatment of estrogen-dependent disease.
J Med Chem, 34 (2): 725-36. [PMID:1825337]
2. LaSala D, Shibanaka Y, Jeng AY. (2009)
Coexpression of CYP11B2 or CYP11B1 with adrenodoxin and adrenodoxin reductase for assessing the potency and selectivity of aldosterone synthase inhibitors.
Anal Biochem, 394 (1): 56-61. [PMID:19622340]
3. Pignatti E, Kollar J, Hafele E, Schuster D, Steele RE, Vogt B, Schumacher C, Groessl M. (2023)
Structural and clinical characterization of CYP11B2 inhibition by dexfadrostat phosphate.
J Steroid Biochem Mol Biol, 235: 106409. [PMID:37827219]
4. Raats JI, Falkson G, Falkson HC. (1992)
A study of fadrozole, a new aromatase inhibitor, in postmenopausal women with advanced metastatic breast cancer.
J Clin Oncol, 10 (1): 111-6. [PMID:1530798]