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Details

Stereochemistry ABSOLUTE
Molecular Formula C21H28O2
Molecular Weight 312.4458
Optical Activity UNSPECIFIED
Defined Stereocenters 6 / 6
E/Z Centers 0
Charge 0

SHOW SMILES / InChI
Structure of TIBOLONE

SMILES

[H][C@@]12CC[C@@](O)(C#C)[C@@]1(C)CC[C@]3([H])C4=C(C[C@@H](C)[C@@]23[H])CC(=O)CC4

InChI

InChIKey=WZDGZWOAQTVYBX-XOINTXKNSA-N
InChI=1S/C21H28O2/c1-4-21(23)10-8-18-19-13(2)11-14-12-15(22)5-6-16(14)17(19)7-9-20(18,21)3/h1,13,17-19,23H,5-12H2,2-3H3/t13-,17-,18+,19-,20+,21+/m1/s1

HIDE SMILES / InChI

Molecular Formula C21H28O2
Molecular Weight 312.4458
Charge 0
Count
Stereochemistry ABSOLUTE
Additional Stereochemistry No
Defined Stereocenters 6 / 6
E/Z Centers 0
Optical Activity UNSPECIFIED

Description
Curator's Comment: Description was created based on several sources, including http://www.ncbi.nlm.nih.gov/pubmed/21942642

Tibolone (brand name Livial, Tibofem), also known as 7α-methylnoretynodrel, is a synthetic steroid drug with estrogenic, progestogenic, and weak androgenic actions which was introduced in 1988 and is used widely in Europe, Asia, Australasia, and, with the exception of the United States (where it is not available), the rest of the world. It is used mainly for treatment of endometriosis, as well as for the treatment of symptoms resulting from the natural or surgical menopause in post menopausal women. Women above 60 years of age should only start with LIVIAL treatment when they are intolerant of or contraindicated for other medicinal products approved for the treatment of oestrogen deficiency symptoms. Tibolone is used for the prevention of bone mineral density loss in postmenopausal women at high risk of future osteoporotic fractures who are intolerant of, or contraindicated for, other medicinal products approved for the prevention of bone mineral density loss. Tibolone has similar or greater efficacy compared to older hormone replacement drugs, but shares a similar side effect profile. It has also been investigated as a possible treatment for female sexual dysfunction. Tibolone is a 19-nortestosterone derivative and is related structurally to other 19-nortestosterone progestins. It is the 7α-methyl derivative of noretynodrel. Tibolone possesses a complex pharmacology. Its two major active metabolites, 3α-hydroxytibolone and 3β-hydroxytibolone, act as potent, fully activating agonists of the estrogen receptor (ER), with a high preference for ERα. Tibolone and its metabolite Δ-tibolone act as agonists of the progesterone and androgen receptors, while 3α-hydroxytibolone and 3β-hydroxytibolone, conversely, act as antagonists of these receptors. Lastly, tibolone, 3α-hydroxytibolone, and 3β-hydroxytibolone act as antagonists of the glucocorticoid and mineralocorticoid receptors, with preference for the mineralocorticoid receptor.

Originator

Curator's Comment: Tibolone was designed in 1964 and patented in 1965 by Organon

Approval Year

Targets

Targets

Primary TargetPharmacologyConditionPotency
4.0 nM [EC50]
105.0 nM [EC50]
123.0 nM [EC50]
170.0 nM [IC50]
1.05 nM [EC50]
Conditions

Conditions

ConditionModalityTargetsHighest PhaseProduct
Primary
Livial

Approved Use

Treatment of symptoms resulting from the natural or surgical menopause in post menopausal women

Launch Date

9.1471682E11
Preventing
Livial

Approved Use

Prevention of bone mineral density loss in postmenopausal women at high risk of future osteoporotic fractures

Launch Date

9.1471682E11
PubMed

PubMed

TitleDatePubMed
[Our experience in the treatment of climacteric complaints with Livial (Organon)].
2001
Effects of 8 years of treatment with tibolone 2.5 mg daily on postmenopausal bone loss.
2001
The management of osteoporosis.
2001 Apr
Short-term effects of three continuous hormone replacement therapy regimens on platelet tritiated imipramine binding and mood scores: a prospective randomized trial.
2001 Apr
[Effect of hormone replacement with tibolone on plasma insulin and blood glucose in postmenopause].
2001 Aug
Effect of hormone replacement therapies and selective estrogen receptor modulators in postmenopausal women with uterine leiomyomas: a literature review.
2001 Dec
Tibolone: new type of hormone replacement.
2001 Dec
Lowering of HDL cholesterol in post-menopausal women by tibolone is not associated with changes in cholesterol efflux capacity or paraoxonase activity.
2001 Dec
Effects of physical activity and menopausal hormone replacement therapy on postural stability in postmenopausal women--a cross-sectional study.
2001 Jan 31
The selective estrogen enzyme modulator (SEEM) in breast cancer.
2001 Jan-Mar
Venous endothelial function in postmenopausal women after six months of tibolone therapy.
2001 Jul 25
Thyroid carcinoma after successful treatment of osteosarcoma: a report of three patients.
2001 Jun-Jul
Effects of estrogen/androgen therapy on bone mineral density parameters.
2001 Mar
Hemodynamic response to tibolone in reproductive and nonreproductive tissues in the sheep.
2001 Mar
Differential effects on the androgen status of postmenopausal women treated with tibolone and continuous combined estradiol and norethindrone acetate replacement therapy.
2001 Mar
Effect of tibolone and raloxifene on the tail temperature of oestrogen-deficient rats.
2001 May 4
[Effect of tibolone on vascular markers of human female coronary arteries - comparison with estradiol/norethisterone].
2001 Nov
The effect of tibolone on fat mass, fat-free mass, and total body water in postmenopausal women.
2001 Nov
A pilot study of hormone replacement therapy with tibolone in women with mastopathic breasts.
2001 Nov 30
Effects of different types of hormone replacement therapy on mammographic density.
2001 Nov 30
Mammographic density increase in women receiving different hormone replacement regimens.
2001 Nov 30
Prevention of bone loss with tibolone in postmenopausal women: results of two randomized, double-blind, placebo-controlled, dose-finding studies.
2001 Oct
Long term effects of Tibolone on postmenopausal women with uterine myomas.
2001 Oct 31
[New gestagens--advantages and disadvantages].
2001 Sep
Tibolone exerts its protective effect on trabecular bone loss through the estrogen receptor.
2001 Sep
Mammographic density changes during different postmenopausal hormone replacement therapies.
2001 Sep
Assessment of the effectiveness of postmenopausal tibolone therapy on neural functions by measuring visual evoked potentials: a placebo-controlled study.
2001 Sep
Comparison of the antiatherosclerotic effect of tibolone with that of estradiol and ethinyl estradiol in cholesterol-fed, ovariectomized rabbits.
2001 Summer
Antiatherosclerotic effects of tibolone.
2001 Summer
Effects of tibolone on plasma homocysteine levels in postmenopausal women.
2002 Aug
Selective modulation of sex steroids.
2002 Feb
Effect of renal impairment on the pharmacokinetics of a single oral dose of tibolone 2.5 mg in early postmenopausal women.
2002 Feb
Tibolone and 5alpha-dihydrotestosterone alone or in combination with an antiandrogen in a rat breast tumour model.
2002 Feb
Cognitive effects of 10 years of hormone-replacement therapy with tibolone.
2002 Feb
Effect of tibolone compared with sequential hormone replacement therapy on carbohydrate metabolism in postmenopausal women.
2002 Feb 26
Dose proportionality of three different doses of tibolone.
2002 Jan
The influence of tibolone on quality of life in postmenopausal women.
2002 Jan 30
Novel therapeutic options for osteoporosis.
2002 Jul
Estrogenic effects of 7alpha-methyl-17alpha-ethynylestradiol: a newly discovered tibolone metabolite.
2002 Jul
Formation of 7 alpha-methyl-ethinyl estradiol during treatment with tibolone.
2002 Jul-Aug
Comparative effects of tibolone and conjugated equine estrogens with and without medroxyprogesterone acetate on the reproductive tract of female cynomolgus monkeys.
2002 Jul-Aug
Randomized, double-masked, 2-year comparison of tibolone with 17beta-estradiol and norethindrone acetate in preventing postmenopausal bone loss.
2002 Mar
A randomized, open-label study of conjugated equine estrogens plus medroxyprogesterone acetate versus tibolone: effects on symptom control, bleeding pattern, lipid profile and tolerability.
2002 Mar
Mammographic changes associated with raloxifene and tibolone therapy in postmenopausal women: a prospective study.
2002 Mar-Apr
Hormone replacement therapy and breast tissue density on mammography.
2002 Mar-Apr
Menopause. HRT: looking for something better.
2002 May
A cross-sectional study of the effects of hormon replacement therapy on the cardiovascular disease risk profile in healthy postmenopausal women.
2002 May
The effects of tibolone on mood and libido.
2002 May-Jun
Patents

Sample Use Guides

Treatment of symptoms resulting from the natural or surgical menopause: The recommended dose is 2.5 mg once daily. Prevention of post-menopausal bone mineral density loss: The recommended dose is 2.5 mg once daily. No dose adjustment is necessary for the elderly. The tablets should be swallowed with some water or other drink, preferably at the same time of day. Improvement of symptoms generally occurs within a few weeks, but optimal results are obtained when therapy is continued for at least 3 months.
Route of Administration: Oral
In Vitro Use Guide
Curator's Comment: The effect of tibolone on invasion was evaluated in the chick heart invasion assay using MCF-7/6 cells and in the collagen type I invasion assay using T47-D cells.
At a concentration of 100 uM, tibolone and its 3beta-OH metabolite possess anti-invasive activities in the two different invasion assays.
Substance Class Chemical
Created
by admin
on Fri Dec 15 15:21:22 UTC 2023
Edited
by admin
on Fri Dec 15 15:21:22 UTC 2023
Record UNII
FF9X0205V2
Record Status Validated (UNII)
Record Version
  • Download
Name Type Language
TIBOLONE
EP   INN   JAN   MART.   MI   USAN   VANDF   WHO-DD  
USAN   INN  
Official Name English
TIBOLONE [EP IMPURITY]
Common Name English
tibolone [INN]
Common Name English
TIBOLONE [USAN]
Common Name English
TIBOLONE [MI]
Common Name English
TIBOLONE [EP MONOGRAPH]
Common Name English
ORG OD 14
Code English
17-Hydroxy-7α-methyl-19-nor-17α-pregn-5(10)-en-20-yn-3-one
Common Name English
19-NORPREGN-5(10)-EN-20-YN-3-ONE, 17-HYDROXY-7-METHYL-, (7.ALPHA.,17.ALPHA.)-
Common Name English
NSC-759898
Code English
ORG-OD 14
Code English
TIBOLONE [JAN]
Common Name English
TIBOLONE [MART.]
Common Name English
TIBOLONE [VANDF]
Common Name English
Tibolone [WHO-DD]
Common Name English
Classification Tree Code System Code
NCI_THESAURUS C2360
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
LIVERTOX NBK548180
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
WHO-ATC G03CX01
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
WHO-VATC QG03CX01
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
Code System Code Type Description
NCI_THESAURUS
C66955
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
DRUG CENTRAL
2655
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
CAS
5630-53-5
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
MERCK INDEX
m10852
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY Merck Index
INN
2777
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
RXCUI
38260
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY RxNorm
DRUG BANK
DB09070
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
WIKIPEDIA
TIBOLONE
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
ChEMBL
CHEMBL2103774
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
NSC
759898
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
PUBCHEM
444008
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
MESH
C027385
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
CHEBI
32223
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
EVMPD
SUB11022MIG
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
FDA UNII
FF9X0205V2
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
SMS_ID
100000092534
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
ECHA (EC/EINECS)
227-069-1
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
EPA CompTox
DTXSID5023667
Created by admin on Fri Dec 15 15:21:22 UTC 2023 , Edited by admin on Fri Dec 15 15:21:22 UTC 2023
PRIMARY
Related Record Type Details
TARGET -> AGONIST
Related Record Type Details
METABOLITE ACTIVE -> PARENT
METABOLITE ACTIVE -> PARENT
METABOLITE ACTIVE -> PARENT
Related Record Type Details
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
IMPURITY -> PARENT
CHROMATOGRAPHIC PURITY (HPLC/UV)
EP
Related Record Type Details
ACTIVE MOIETY