General
Preferred name
FORMESTANE
Synonyms
CGP-32349 ()
NSC 282175 ()
CGP-32349, NSC 282175 ()
4-oh-androstene-3,17-dione ()
NSC-282175 ()
Lentaron ()
CGP 32349 ()
4-hydroxy Androstenedione ()
P&D ID
PD009176
CAS
566-48-3
Tags
natural product
drug
available
First approval
1993
Drug Status
investigational
approved
withdrawn
Drug indication
Breast cancer
Max Phase
Phase 4
Structure
Probe scores
P&D probe-likeness score
[[ v.score ]]%
Structure formats
[[ format ]]
[[ compound[format === 'MOL' ? 'molblock' : format.toLowerCase()] ]]
Description
(extracted from source data)
ABSORPTION 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. [2]
PHARMACODYNAMICS 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. [3]; ; 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. [5]
MOA 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.
METABOLISM 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.
Cell lines
6
Organisms
1
Compound Sets
13
Cayman Chemical Bioactives
18282
ChEMBL Approved Drugs
CHEMBL132530
ChEMBL Drugs
CHEMBL132530
DrugBank
DB08905
DrugBank Approved Drugs
DB08905
DrugCentral
1238
DrugCentral Approved Drugs
1238
DrugMAP
DMWIDJK
NPC Screening Collection
Prestwick Chemical Library
Selleckchem Bioactive Compound Library
Formestane
TargetMol Bioactive Compound Library
T1099
Withdrawn 2.0
DB08905
External IDs
26
Properties
(calculated by RDKit )
Molecular Weight
302.19
Hydrogen Bond Acceptors
3
Hydrogen Bond Donors
1
Rotatable Bonds
0
Ring Count
4
Aromatic Ring Count
0
cLogP
3.97
TPSA
54.37
Fraction CSP3
0.79
Chiral centers
5.0
Largest ring
6.0
QED
0.74
Structural alerts
0
No structural alerts detected
Related compounds
Custom attributes
(extracted from source data)
Pathway
Endocrinology/Hormones
Target
Aromatase
ATC
L02BG02
Source data