- Generic Name
- DrugBank Accession Number
Formestane was the first selective, type I, steroidal aromatase inhibitor used in the treatment of estrogen-receptor positive breast cancer in post-menopausal women. Formestane suppresses estrogen production from anabolic steroids or prohormones. Formestane is also a prohormone of 4-hydroxytestosterone, an active steroid with weak androgenic activity and mild aromatase inhibitor activity. It is listed as a prohibited substance by the World Anti-Doping Agency for use in athletes.
Formestane has poor oral bioavailability, and thus must be administered fortnightly (bi-weekly) by intramuscular injection. Some clinical data has suggested that the clinically recommended dose of 250mg was too low. With the discovery of newer, non-steroidal and steroidal, aromatase inhibitors which were orally active and less expensive than formestane, formestane lost popularity.
Currently, formestane (categorized as an anti-estrogenic agent) is prohibited from use in sports in accordance to the regulations of the World Anti-Doping Agency. It is not US FDA approved, and the intramuscular injection form of formestane (Lentaron) which was approved in Europe has been withdrawn.
- Small Molecule
- Approved, Investigational, Withdrawn
- Average: 302.4079
- Chemical Formula
- External IDs
- CGP 32349
For the treatment of estrogen-receptor positive breast cancer in post-menopausal women.Reduce drug development failure ratesBuild, train, & validate machine-learning modelswith evidence-based and structured datasets.Build, train, & validate predictive machine-learning models with structured datasets.
- Contraindications & Blackbox Warnings
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By significantly reducing estrogen levels in the bloodstream, formestane may exhibit antitumor activity.
In one trial involving 147 postmenopausal females with advanced breast cancers resistant to standard therapies, 22% of patients achieved a partial response, while another 20% achieved disease stabilization. 
In comparative trials comparing a non-steroidal aromatase inhibitor, anastrozole, with formestane, it was found that anastrozole was more effective and consistent at suppressing estrogen levels in the body. However, these results were of unverified clinical significance. 
- Mechanism of action
Formestane is a second generation, irreversible, steroidal aromatase inhibitor. It inhibits the aromatase enzyme responsible for converting androgens to estrogens, thereby preventing estrogen production.
Breast cancer may be estrogen sensitive or insensitive. A majority of breast cancers are estrogen sensitive. Estrogen sensitive breast cancer cells depend on estrogen for viability. Thus removal of estrogen from the body can be an effective treatment for hormone sensitive breast cancers.
Formestane has been targeted specifically for the treatment of postmenopausal women. Unlike premenopausal women who produce most estrogen in the ovaries, postmenopausal women produce most estrogen in peripheral tissues with the help of the aromatase enzyme. Formestane, an aromatase inhibitor, can thus help to decrease the local production of estrogen by blocking the aromatase enzyme in peripheral tissues (ie. adispose tissue of the breast) to treat hormone sensitive breast cancer.
Formestane has poor oral bioavailability, but is fully bioavailable when administered via the established intramuscular route. The AUC after an intravenous pulse dose does not vary considerably from that of an intramuscular dose.
Within 24-48 h of the first dose of intramuscular formestane, a C(max) of 48.0 +/- 20.9 nmol/l was achieved in one study. 
- Volume of distribution
Vd = 1.8 L/kg; widely distributed to organs and tissues when delivered intravenously. 
- Protein binding
Hepatic metabolism. Phase I of metabolism is mainly reductive in nature. The reduction products 3 beta-hydroxy-5alpha-androstane-4,17-dione and 3alpha-hydroxy-5beta-androstane-4,17-dione are produced, and further reduced. A notable step in the process of metabolism is a keto reduction on carbon number three of the molecule. The main metabolite which is produced from formestane is 4-hydroyxyandrost-4-ene-3,17-dione-4-glucuronide.
The oxidation products identified were 4-hydroxyandrosta-4,6-diene-3,17-dione and 4-hydroxyandrosta-1,4-diene-3,17-dione.
In phase II, conjugation was diverse and included sulfatation and glucuronidation. 4-hydroxytestosterone, the 17-hydroxylated analog to formestane, was identified as one particular metabolite found in women's urine. This finding was the result of an oral administration of 500mg of formestane in women.
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- Route of elimination
Renal elimination. >95% in urine, <5% in feces.
Terminal plasma elimination half life of 18 minutes, when delivered intravenously. 
Plasma clearance is approximately 4.2 L/(h kg), when delivered intravenously.
In women, following a 500mg dose of formestane, 20% was excreted as glucuronide within the first 24 hours. 
One long term metabolite (3beta,4alpha-dihydroxy-5alpha-androstan-17-one) can be detected for 90 hours. A longer detection time is possible with more sensitive technology, which may be of utility in sports drug testing. 
- Adverse Effects
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- Not Available
- Pharmacogenomic Effects/ADRs
- Not Available
- Drug Interactions
- This information should not be interpreted without the help of a healthcare provider. If you believe you are experiencing an interaction, contact a healthcare provider immediately. The absence of an interaction does not necessarily mean no interactions exist.
Drug Interaction Abacavir Abacavir may decrease the excretion rate of Formestane which could result in a higher serum level. Abemaciclib The metabolism of Abemaciclib can be increased when combined with Formestane. Acalabrutinib The metabolism of Acalabrutinib can be increased when combined with Formestane. Aceclofenac Aceclofenac may decrease the excretion rate of Formestane which could result in a higher serum level. Acemetacin Acemetacin may decrease the excretion rate of Formestane which could result in a higher serum level. Acenocoumarol The metabolism of Acenocoumarol can be increased when combined with Formestane. Acetaminophen Acetaminophen may decrease the excretion rate of Formestane which could result in a higher serum level. Acetazolamide Acetazolamide may increase the excretion rate of Formestane which could result in a lower serum level and potentially a reduction in efficacy. Acetylsalicylic acid Acetylsalicylic acid may decrease the excretion rate of Formestane which could result in a higher serum level. Aclidinium Aclidinium may decrease the excretion rate of Formestane which could result in a higher serum level.Identify potential medication risksEasily compare up to 40 drugs with our drug interaction checker.Get severity rating, description, and management advice.Learn more
- Food Interactions
- Not Available
- Drug product information from 10+ global regionsOur datasets provide approved product information including:dosage, form, labeller, route of administration, and marketing period.Access drug product information from over 10 global regions.
- Mixture Products
Name Ingredients Dosage Route Labeller Marketing Start Marketing End Region Image Lentaron Formestane (250 mg / kit) + Sodium chloride (.9 % / kit) Liquid; Powder, for solution Intramuscular Novartis 1994-12-31 1999-08-04
- ATC Codes
- L02BG02 — Formestane
- Drug Categories
- Adrenal Cortex Hormones
- Antineoplastic Agents
- Antineoplastic and Immunomodulating Agents
- Aromatase Inhibitors
- Cytochrome P-450 CYP3A Inducers
- Cytochrome P-450 CYP3A4 Inducers
- Cytochrome P-450 CYP3A4 Inducers (strength unknown)
- Cytochrome P-450 Enzyme Inducers
- Drugs that are Mainly Renally Excreted
- Endocrine Therapy
- Enzyme Inhibitors
- Estrogen Antagonists
- Fused-Ring Compounds
- Gonadal Hormones
- Gonadal Steroid Hormones
- Hormone Antagonists
- Hormone Antagonists and Related Agents
- Hormones, Hormone Substitutes, and Hormone Antagonists
- Steroid Synthesis Inhibitors
- Testosterone Congeners
- Chemical TaxonomyProvided by Classyfire
- This compound belongs to the class of organic compounds known as androgens and derivatives. These are 3-hydroxylated C19 steroid hormones. They are known to favor the development of masculine characteristics. They also show profound effects on scalp and body hair in humans.
- Organic compounds
- Super Class
- Lipids and lipid-like molecules
- Steroids and steroid derivatives
- Sub Class
- Androstane steroids
- Direct Parent
- Androgens and derivatives
- Alternative Parents
- Hydroxysteroids / 3-oxo delta-4-steroids / 17-oxosteroids / Delta-4-steroids / Cyclohexenones / Enols / Organic oxides / Hydrocarbon derivatives
- 17-oxosteroid / 3-oxo-delta-4-steroid / 3-oxosteroid / 4-hydroxysteroid / Aliphatic homopolycyclic compound / Androgen-skeleton / Carbonyl group / Cyclic ketone / Cyclohexenone / Delta-4-steroid
- Molecular Framework
- Aliphatic homopolycyclic compounds
- External Descriptors
- enol, 3-oxo Delta(4)-steroid, 17-oxo steroid, hydroxy steroid (CHEBI:75172)
- Affected organisms
- Not Available
- CAS number
- InChI Key
- IUPAC Name
- Synthesis Reference
Kohler, Maxie, et al. "Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites." Steroids 72.3 (2007): 278-286.
- General References
- Perez Carrion R, Alberola Candel V, Calabresi F, Michel RT, Santos R, Delozier T, Goss P, Mauriac L, Feuilhade F, Freue M, et al.: Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. Ann Oncol. 1994;5 Suppl 7:S19-24. [Article]
- Kohler M, Parr MK, Opfermann G, Thevis M, Schlorer N, Marner FJ, Schanzer W: Metabolism of 4-hydroxyandrostenedione and 4-hydroxytestosterone: Mass spectrometric identification of urinary metabolites. Steroids. 2007 Mar;72(3):278-86. Epub 2007 Jan 17. [Article]
- Lonning PE, Geisler J, Johannessen DC, Gschwind HP, Waldmeier F, Schneider W, Galli B, Winkler T, Blum W, Kriemler HP, Miller WR, Faigle JW: Pharmacokinetics and metabolism of formestane in breast cancer patients. J Steroid Biochem Mol Biol. 2001 Apr;77(1):39-47. [Article]
- Murray R, Pitt P: Treatment of advanced breast cancer with formestane. Ann Oncol. 1994;5 Suppl 7:S11-3. [Article]
- Vorobiof DA, Kleeberg UR, Perez-Carrion R, Dodwell DJ, Robertson JF, Calvo L, Dowsett M, Clack G: A randomized, open, parallel-group trial to compare the endocrine effects of oral anastrozole (Arimidex) with intramuscular formestane in postmenopausal women with advanced breast cancer. Ann Oncol. 1999 Oct;10(10):1219-25. [Article]
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- Not Available
- Not Available
- Dosage Forms
Form Route Strength Liquid; powder, for solution Intramuscular
- Not Available
- Not Available
- Experimental Properties
Property Value Source melting point (°C) 199 - 202 MSDS water solubility Insoluble MSDS logP 2.66 MSDS pKa 9.31 MSDS
- Predicted Properties
Property Value Source Water Solubility 0.0578 mg/mL ALOGPS logP 2.57 ALOGPS logP 3.41 Chemaxon logS -3.7 ALOGPS pKa (Strongest Acidic) 9.21 Chemaxon pKa (Strongest Basic) -3.7 Chemaxon Physiological Charge 0 Chemaxon Hydrogen Acceptor Count 3 Chemaxon Hydrogen Donor Count 1 Chemaxon Polar Surface Area 54.37 Å2 Chemaxon Rotatable Bond Count 0 Chemaxon Refractivity 85.57 m3·mol-1 Chemaxon Polarizability 34.05 Å3 Chemaxon Number of Rings 4 Chemaxon Bioavailability 1 Chemaxon Rule of Five Yes Chemaxon Ghose Filter Yes Chemaxon Veber's Rule No Chemaxon MDDR-like Rule No Chemaxon
- Predicted ADMET Features
Property Value Probability Human Intestinal Absorption + 1.0 Blood Brain Barrier + 0.9628 Caco-2 permeable + 0.8149 P-glycoprotein substrate Substrate 0.6597 P-glycoprotein inhibitor I Inhibitor 0.7113 P-glycoprotein inhibitor II Non-inhibitor 0.8526 Renal organic cation transporter Non-inhibitor 0.7227 CYP450 2C9 substrate Non-substrate 0.8331 CYP450 2D6 substrate Non-substrate 0.9308 CYP450 3A4 substrate Substrate 0.753 CYP450 1A2 substrate Non-inhibitor 0.9046 CYP450 2C9 inhibitor Non-inhibitor 0.9443 CYP450 2D6 inhibitor Non-inhibitor 0.941 CYP450 2C19 inhibitor Non-inhibitor 0.9025 CYP450 3A4 inhibitor Non-inhibitor 0.85 CYP450 inhibitory promiscuity Low CYP Inhibitory Promiscuity 0.9027 Ames test Non AMES toxic 0.9311 Carcinogenicity Non-carcinogens 0.9537 Biodegradation Not ready biodegradable 0.963 Rat acute toxicity 1.6135 LD50, mol/kg Not applicable hERG inhibition (predictor I) Weak inhibitor 0.9479 hERG inhibition (predictor II) Non-inhibitor 0.7566
- Mass Spec (NIST)
- Not Available
Spectrum Spectrum Type Splash Key Predicted MS/MS Spectrum - 10V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Positive (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 10V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 20V, Negative (Annotated) Predicted LC-MS/MS Not Available Predicted MS/MS Spectrum - 40V, Negative (Annotated) Predicted LC-MS/MS Not Available MS/MS Spectrum - , positive LC-MS/MS splash10-01t9-2920000000-24696d73561fe3ce6680
- Pharmacological action
- General Function
- Vitamin d3 25-hydroxylase activity
- Specific Function
- Cytochromes P450 are a group of heme-thiolate monooxygenases. In liver microsomes, this enzyme is involved in an NADPH-dependent electron transport pathway. It performs a variety of oxidation react...
- Gene Name
- Uniprot ID
- Uniprot Name
- Cytochrome P450 3A4
- Molecular Weight
- 57342.67 Da
- Blog [Link]
Drug created at June 14, 2013 04:20 / Updated at February 21, 2021 18:52