TIBOLONE

Possibly Marketed Outside US

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 Search

SMILES

C[C@@H]1CC2=C(CCC(=O)C2)[C@H]3CC[C@@]4(C)[C@@H](CC[C@@]4(O)C#C)[C@H]13

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
Sources: http://www.medsafe.govt.nz/profs/datasheet/l/Livialtab.pdf
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.

CNS Activity

Originator

Approval Year

Targets

Primary Target	Pharmacology	Potency
Steryl-sulfatase 33 Target ID: CHEMBL3559 Sources: http://www.ncbi.nlm.nih.gov/pubmed/11832993	Inhibitor 8504
Estrogen receptor alpha 134 Target ID: CHEMBL206 Sources: http://www.ncbi.nlm.nih.gov/pubmed/19464167	Agonist 2752	4.0 nM [EC50]
Estrogen receptor beta 113 Target ID: CHEMBL242 Sources: http://www.ncbi.nlm.nih.gov/pubmed/19464167	Agonist 2752	105.0 nM [EC50]
Progesterone receptor 61 Target ID: CHEMBL208 Sources: http://www.ncbi.nlm.nih.gov/pubmed/19464167	Agonist 2752	123.0 nM [EC50]
Mineralocorticoid receptor 53 Target ID: CHEMBL1994 Sources: http://www.ncbi.nlm.nih.gov/pubmed/19464167	Antagonist 2849	170.0 nM [IC50]
Androgen Receptor 169 Target ID: CHEMBL1871 Sources: http://www.ncbi.nlm.nih.gov/pubmed/19464167	Agonist 2752	1.05 nM [EC50]

Conditions

Condition	Modality	Targets	Highest Phase	Product
Menopausal syndrome 6 Sources: http://www.medsafe.govt.nz/profs/datasheet/l/Livialtab.pdf	Primary		Approved 8583	Livial Approved Use Treatment of symptoms resulting from the natural or surgical menopause in post menopausal women Launch Date 1998
Postmenopausal osteoporosis 59 Sources: http://www.medsafe.govt.nz/profs/datasheet/l/Livialtab.pdf	Preventing		Approved 8583	Livial Approved Use Prevention of bone mineral density loss in postmenopausal women at high risk of future osteoporotic fractures Launch Date 1998

C_max

Value	Dose	Analyte	Population
0.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	TIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
1.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	TIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
1.5 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	TIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
1.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	TIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
8.3 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
10.9 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
14.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
16.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
2.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
2.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
2.1 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
3.7 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
1.44 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	TIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
1.47 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	TIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: HIGH-FAT
12.97 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
9.6 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: HIGH-FAT
3.77 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
3.22 ng/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: HIGH-FAT

AUC

Value	Dose	Analyte	Population
24.6 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
29.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
45.4 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
55.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
6.2 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
5.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
5.7 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
10.9 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
45.04 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
47.78 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: HIGH-FAT
15.36 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
17.38 ng × h/mL EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: HIGH-FAT

T_1/2

Value	Dose	Analyte	Population
6.4 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
5.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
5.7 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
6 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
6.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
6.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	1.25 mg single, oral dose: 1.25 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
6.2 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
5.9 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/12207627/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
5.32 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
4.96 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.ALPHA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: HIGH-FAT
5.61 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: FASTED
5.08 h EXPERIMENT https://pubmed.ncbi.nlm.nih.gov/11899948/	2.5 mg single, oral dose: 2.5 mg route of administration: Oral experiment type: SINGLE co-administered:	3.BETA.-HYDROXYTIBOLONE plasma	Homo sapiens population: HEALTHY age: ADULT sex: FEMALE food status: HIGH-FAT

Doses

Dose	Population	Adverse events
2.5 mg 2 times / day multiple, oral Higher than recommended Dose: 2.5 mg, 2 times / day Route: oral Route: multiple Dose: 2.5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6992927/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6992927/	Disc. AE: Uterine bleeding... AEs leading to discontinuation/dose reduction: Uterine bleeding (12%) Sources: https://pubmed.ncbi.nlm.nih.gov/6992927/
5 mg 1 times / day multiple, oral Highest studied dose Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12387462/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12387462/	Disc. AE: Vaginal bleeding... Other AEs: Embolism, Cholecystitis... AEs leading to discontinuation/dose reduction: Vaginal bleeding (0.7%) Other AEs: Embolism Cholecystitis Sources: https://pubmed.ncbi.nlm.nih.gov/12387462/
2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17607296/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17607296/	Disc. AE: Drug-induced hepatitis... AEs leading to discontinuation/dose reduction: Drug-induced hepatitis Sources: https://pubmed.ncbi.nlm.nih.gov/17607296/

AEs

AE	Significance	Dose	Population
Uterine bleeding	12% Disc. AE	2.5 mg 2 times / day multiple, oral Higher than recommended Dose: 2.5 mg, 2 times / day Route: oral Route: multiple Dose: 2.5 mg, 2 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/6992927/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/6992927/
Cholecystitis		5 mg 1 times / day multiple, oral Highest studied dose Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12387462/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12387462/
Embolism		5 mg 1 times / day multiple, oral Highest studied dose Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12387462/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12387462/
Vaginal bleeding	0.7% Disc. AE	5 mg 1 times / day multiple, oral Highest studied dose Dose: 5 mg, 1 times / day Route: oral Route: multiple Dose: 5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/12387462/	healthy, ADULT Health Status: healthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/12387462/
Drug-induced hepatitis	Disc. AE	2.5 mg 1 times / day multiple, oral Recommended Dose: 2.5 mg, 1 times / day Route: oral Route: multiple Dose: 2.5 mg, 1 times / day Sources: https://pubmed.ncbi.nlm.nih.gov/17607296/	unhealthy, ADULT Health Status: unhealthy Age Group: ADULT Sex: F Food Status: UNKNOWN Sources: https://pubmed.ncbi.nlm.nih.gov/17607296/

Overview

CYP3A4	CYP2C9	CYP2D6	hERG
inhibitor 2252	inhibitor 2438	inhibitor 2507	inhibitor 2217

OverviewOther

Other Inhibitor	Other Substrate	Other Inducer
CYP1A2 2153 CYP3A 227 CYP2E1 1060 CYP19A 1 CYP2C19 2057 P-gp 1741	SULT2A1 28 SULT1E1 22 CYP 303 SULT2B1b 2 3-beta-HSD 3 SULT1B1 8 SULT1C2 3 AKR1C4 7 SULT1A1 37 SULT1A3 31 AKR1C1 22 AKR1C2 12

Drug as perpetrator

Target	Modality	Activity	Metabolite
P-gp 1932	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1346987#sid=144205803	inconclusive [IC50 18.3564 uM]
CYP3A4 2633	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1671201#sid=170465874	inconclusive [IC50 3.0901 uM]
CYP2D6 2546	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/1645840#sid=170465874	inconclusive [IC50 38.9018 uM]
CYP2E1 1146	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11792677/	no
CYP19A 1	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17467267/	yes [IC50 28 uM]	Delta4-isotibolone 1
CYP2C19 2141	inhibitor 4027 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/625247#sid=160692461	yes [IC50 3 uM]
CYP19A 1	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/17467267/	yes [IC50 42 uM]
CYP1A2 2333	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11792677/	yes [Ki 100 uM]
CYP3A 317	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11792677/	yes [Ki 14.5 uM]
CYP2C9 2497	inhibitor 4027 Sources: https://pubmed.ncbi.nlm.nih.gov/11792677/	yes [Ki 14.8 uM]

Drug as victim

Target	Modality	Activity	Metabolite
CYP 303	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/11792677/	minor
SULT1A1 37	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	no
SULT1A3 31	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	no
SULT1B1 8	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	no
SULT1C2 3	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	no
SULT1E1 22	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	no	Delta4-isotibolone 1
SULT2B1b 2	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	no
SULT2B1b 2	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	no	Delta4-isotibolone 1
SULT1E1 22	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	yes [IC50 19.5 uM]
AKR1C1 22	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/ \| https://molpharm.aspetjournals.org/content/66/6/1702	yes [Km 0.76 uM]
AKR1C2 12	substrate 4014 Sources: https://molpharm.aspetjournals.org/content/66/6/1702	yes [Km 0.87 uM]
AKR1C4 7	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/ \| https://molpharm.aspetjournals.org/content/66/6/1702	yes [Km 1.06 uM]
SULT2A1 28	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	yes [Km 1.4 uM]	3alpha-OH tibolone 1
SULT1E1 22	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	yes [Km 2.1 uM]	3alpha-OH tibolone 1
SULT2B1b 2	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	yes [Km 3.9 uM]	3alpha-OH tibolone 1
SULT2A1 28	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	yes [Km 4.5 uM]	3beta-OH tibolone 1
SULT2A1 28	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	yes [Km 4.8 uM]
SULT2A1 28	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	yes [Km 6.4 uM]	Delta4-isotibolone 1
SULT1E1 22	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	yes [Km 6.6 uM]	3beta-OH tibolone 1
SULT2B1b 2	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	yes [Km 7.9 uM]	3beta-OH tibolone 1
3-beta-HSD 3	substrate 4014 Sources: https://pubmed.ncbi.nlm.nih.gov/15145448/	yes	3beta-OH tibolone 1

Tox targets

Target	Modality	Activity	Metabolite	Clinical evidence
hERG 2263	inhibitor 2237 Sources: https://pubchem.ncbi.nlm.nih.gov/bioassay/588834#sid=144205803

PubMed

Title	Date	PubMed
[Our experience in the treatment of climacteric complaints with Livial (Organon)].	2001	11803863
Quality of life and sexuality changes in postmenopausal women receiving tibolone therapy.	2001 Dec	11770188
Effect of hormone replacement therapies and selective estrogen receptor modulators in postmenopausal women with uterine leiomyomas: a literature review.	2001 Dec	11770184
Tibolone: new type of hormone replacement.	2001 Dec	11751099
[Effect of tibolone on vascular markers of human female coronary arteries - comparison with estradiol/norethisterone].	2001 Nov	11797164
The effect of tibolone on fat mass, fat-free mass, and total body water in postmenopausal women.	2001 Nov	11606448
Tibolone versus 17beta-estradiol/norethisterone: effects on the proliferation of human breast cancer cells.	2002	12013108
Effects of tibolone on thromboxane B(2) levels in postmenopausal women.	2002	11803222
Combination treatment of osteoporosis: a clinical review.	2002 Apr	11988132
[Tibolone-induced hepatotoxicity].	2002 Apr	11975880
Effects of tibolone and continuous combined hormone replacement therapy on mammographic breast density.	2002 Apr	11967497
Serum cholesterol efflux potential in postmenopausal monkeys treated with tibolone or conjugated estrogens.	2002 Apr	11912565
Prospective, randomised study with three HRT regimens in postmenopausal women with an intact uterus.	2002 Apr 25	12034516
Effects of tibolone on plasma homocysteine levels in postmenopausal women.	2002 Aug	12137873
Selective modulation of sex steroids.	2002 Feb	12039446
The effect of tibolone on the lipoprotein profile of postmenopausal women with type III hyperlipoproteinemia.	2002 Feb	11908467
Effect of renal impairment on the pharmacokinetics of a single oral dose of tibolone 2.5 mg in early postmenopausal women.	2002 Feb	11837552
Tibolone does not affect muscle power and functional ability in healthy postmenopausal women.	2002 Feb	11834133
Tibolone and 5alpha-dihydrotestosterone alone or in combination with an antiandrogen in a rat breast tumour model.	2002 Feb	11818212
Cognitive effects of 10 years of hormone-replacement therapy with tibolone.	2002 Feb	11799344
Effect of tibolone compared with sequential hormone replacement therapy on carbohydrate metabolism in postmenopausal women.	2002 Feb 26	11836044
Muscle strength and tibolone: a randomised, double-blind, placebo-controlled trial.	2002 Jan	11845814
Inhibition of oestrone sulphatase activity by tibolone and its metabolites.	2002 Jan	11832993
Therapies to improve bone mineral density and reduce the risk of fracture: clinical trial results.	2002 Jan	11829081
Dose proportionality of three different doses of tibolone.	2002 Jan	11794431
The influence of tibolone on quality of life in postmenopausal women.	2002 Jan 30	11809341
Effects of tibolone on the development of osteopenia induced by ovariectomy in rats.	2002 Jan-Feb	12020042
Gateways to clinical trials.	2002 Jan-Feb	11980386
Effects of tibolone on endogenous nitric oxide (nitrite/nitrate levels) in postmenopausal women.	2002 Jan-Feb	11900269
The in vivo metabolism of tibolone in animal species.	2002 Jan-Mar	11996321
Novel therapeutic options for osteoporosis.	2002 Jul	12118183
Estrogenic effects of 7alpha-methyl-17alpha-ethynylestradiol: a newly discovered tibolone metabolite.	2002 Jul	12117614
Hormone replacement therapy and mammographic screening.	2002 Jul	12096852
Bone metabolism in postmenopausal women who were treated with a gonadotropin-releasing hormone agonist and tibolone.	2002 Jul	12095492
Formation of 7 alpha-methyl-ethinyl estradiol during treatment with tibolone.	2002 Jul-Aug	12082366
The role of ERT/HRT.	2002 Jun	12099668
Tibolone: new preparation. Menopausal symptoms: oestrogen-progestogen combinations are still the reference treatment.	2002 Jun	12068842
[Clinical aspects of Livial in postmenopausal replacement therapy].	2002 Mar	12092255
Randomized, double-masked, 2-year comparison of tibolone with 17beta-estradiol and norethindrone acetate in preventing postmenopausal bone loss.	2002 Mar	11991445
[Drugs in development for the treatment of osteoporosis: Tibolone].	2002 Mar	11979954
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	11974560
Effect of a standardized meal on the bioavailability of a single oral dose of tibolone 2.5 mg in healthy postmenopausal women.	2002 Mar	11899948
Therapeutic interventions in osteoporosis.	2002 Mar 7-13	11921627
Mammographic changes associated with raloxifene and tibolone therapy in postmenopausal women: a prospective study.	2002 Mar-Apr	11875329
Hormone replacement therapy and breast tissue density on mammography.	2002 Mar-Apr	11875326
Menopause. HRT: looking for something better.	2002 May	12034554
A cross-sectional study of the effects of hormon replacement therapy on the cardiovascular disease risk profile in healthy postmenopausal women.	2002 May	12009348
Short-term administration of tibolone plus GnRH analog before laparoscopic myomectomy.	2002 May	11960042
The effects of tibolone on mood and libido.	2002 May-Jun	11973439
Replacing hormones, understanding the consequences.	2002 May-Jun	11973437

Patents

Sample Use Guides

In Vivo Use Guide

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

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 `Mon Mar 31 17:55:01 GMT 2025` Edited by `admin` on `Mon Mar 31 17:55:01 GMT 2025`
Record UNII	FF9X0205V2
Record Status	`Validated (UNII)`
Record Version

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Name

Type

Language

TIBOLONE

Official Name

English

NSC-759898

Preferred 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-7?-methyl-19-nor-17?-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

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