Tibolone
drugOn this page
Also known as LivialNSC-759898ORG OD 14ORG-OD 14TibolonaSID144205803SID170465874C0164847
Summary
Tibolone (CHEMBL2103774) is an approved small-molecule hormone agonist (ATC G03CX01) targeting ESR1; indicated across 5 conditions including osteoporosis and physiological sexual disorder.
At a glance
- Status: Approved (max clinical phase 4)
- Modality: Small molecule
- ATC class: G03CX01
- Targets: 1 (ESR1)
- Indications: 5 conditions
- Clinical trials: 21
- Chemistry: 312.4 Da · C21H28O2
Identifiers
Drug identity and classification
| Field | Value |
|---|---|
| ChEMBL ID | CHEMBL2103774 |
| Name | Tibolone |
| Type | Small molecule |
| Max phase | 4 |
| FDA approved | no |
| PubChem CID | 444008 |
| ChEBI | CHEBI:32223 |
| ATC | G03CX01 |
| Molecular formula | C21H28O2 |
| Molecular weight | 312.4 |
| InChIKey | WZDGZWOAQTVYBX-XOINTXKNSA-N |
SMILES: C[C@@H]1CC2=C(CCC(=O)C2)[C@@H]3[C@@H]1[C@@H]4CC[C@]([C@]4(CC3)C)(C#C)O
IUPAC name: (7R,8R,9S,13S,14S,17R)-17-ethynyl-17-hydroxy-7,13-dimethyl-1,2,4,6,7,8,9,11,12,14,15,16-dodecahydrocyclopenta[a]phenanthren-3-one
ChEBI definition: Estran-3-one with a double bond between positions 5 and 10, and bearing both an ethynyl group and a hydroxy group at position 17 (R-configuration). A synthetic steroid hormone drug which acts as an agonist at all five type I steroid hormone receptors, it is used in the prevention of postmenopausal osteoporosis and for treatment of endometriosis.
Pharmacological roles (ChEBI): hormone agonist, bone density conservation agent.
Also known as: Livial, NSC-759898, ORG OD 14, ORG-OD 14, Tibolona, Tibolone, TIBOLONE, SID144205803, tibolone, SID170465874, C0164847
Patent coverage: 1,188 distinct patent families (4,380 SureChEMBL compound mentions), from 1 matched compound structure(s). Mentions count patents naming the compound (not distinct inventions), so promiscuous / reference molecules inflate the mention figure — families are the dedup metric.
Targets
Targets
Primary targets (GtoPdb curated mechanism): the Cancer dependency column is the DepMap CRISPR fitness signal (% of screened cell lines dependent on the target).
| Gene | Target | Action | pAffinity | Cancer dependency | UniProt |
|---|---|---|---|---|---|
| ESR1 | Estrogen receptor-α | Agonist | 8.4 | 1.7% | P03372 |
Broader ChEMBL bioactivity targets: 13 (assay-derived). Sample: Glucocorticoid receptor, Estrogen receptor, Progesterone receptor, Sodium-dependent serotonin transporter, Prostaglandin G/H synthase 2, Kappa-type opioid receptor, Sodium-dependent dopamine transporter, Adenosine receptor A3, 3’,5’-cyclic-AMP phosphodiesterase 4D, Androgen receptor.
Bioactivity
ChEMBL activities: 14 potent at pChembl ≥ 5 of 18 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):
| Target | pChembl | Type | Value | Unit | Activity ID |
|---|---|---|---|---|---|
| SLC6A4 | 7.32 | Ki | 48.2 | nM | CHEMBL_ACT_7810727 |
| P15207 | 7.25 | AC50 | 56 | nM | CHEMBL_ACT_25233144 |
| P15207 | 7.12 | Ki | 75.4 | nM | CHEMBL_ACT_7810739 |
| SLC6A4 | 7.04 | IC50 | 90.7 | nM | CHEMBL_ACT_7810726 |
| P15207 | 6.95 | IC50 | 113 | nM | CHEMBL_ACT_7810738 |
| ESR1 | 6.91 | Ki | 123.8 | nM | CHEMBL_ACT_7808573 |
| NR3C1 | 6.42 | AC50 | 380 | nM | CHEMBL_ACT_25176333 |
| PGR | 6.4 | AC50 | 400 | nM | CHEMBL_ACT_25223455 |
| ESR1 | 6.36 | IC50 | 433.3 | nM | CHEMBL_ACT_7808572 |
| SLC6A4 | 6.1 | AC50 | 800 | nM | CHEMBL_ACT_25150862 |
| CYP2C19 | 5.52 | IC50 | 3000 | nM | CHEMBL_ACT_7808550 |
| Q63921 | 5.35 | AC50 | 4500 | nM | CHEMBL_ACT_25174925 |
| PDE4D | 5.16 | AC50 | 6900 | nM | CHEMBL_ACT_25185880 |
| ADORA3 | 5.09 | AC50 | 8100 | nM | CHEMBL_ACT_25134748 |
Target pathways
Aggregated over 1 target gene(s): ESR1.
Top Reactome pathways
17 total, by targets touching each:
| Pathway | Targets | Genes |
|---|---|---|
| Nuclear signaling by ERBB4 | 1 | ESR1 |
| PIP3 activates AKT signaling | 1 | ESR1 |
| Constitutive Signaling by Aberrant PI3K in Cancer | 1 | ESR1 |
| Nuclear Receptor transcription pathway | 1 | ESR1 |
| SUMOylation of intracellular receptors | 1 | ESR1 |
| Ovarian tumor domain proteases | 1 | ESR1 |
| PI5P, PP2A and IER3 Regulate PI3K/AKT Signaling | 1 | ESR1 |
| TFAP2 (AP-2) family regulates transcription of growth factors and their receptors | 1 | ESR1 |
| RUNX1 regulates estrogen receptor mediated transcription | 1 | ESR1 |
| ESR-mediated signaling | 1 | ESR1 |
| RUNX1 regulates transcription of genes involved in WNT signaling | 1 | ESR1 |
| Regulation of RUNX2 expression and activity | 1 | ESR1 |
| Extra-nuclear estrogen signaling | 1 | ESR1 |
| Estrogen-dependent gene expression | 1 | ESR1 |
| Mitochondrial unfolded protein response (UPRmt) | 1 | ESR1 |
| Developmental Lineage of Mammary Gland Luminal Epithelial Cells | 1 | ESR1 |
| Developmental Lineage of Mammary Gland Alveolar Cells | 1 | ESR1 |
Dominant GO biological processes
| GO term | Targets |
|---|---|
| negative regulation of transcription by RNA polymerase II | 1 |
| antral ovarian follicle growth | 1 |
| epithelial cell development | 1 |
| chromatin remodeling | 1 |
| regulation of DNA-templated transcription | 1 |
| regulation of transcription by RNA polymerase II | 1 |
| signal transduction | 1 |
| phospholipase C-activating G protein-coupled receptor signaling pathway | 1 |
| positive regulation of cytosolic calcium ion concentration | 1 |
| androgen metabolic process | 1 |
| male gonad development | 1 |
| negative regulation of gene expression | 1 |
| nuclear receptor-mediated steroid hormone signaling pathway | 1 |
| estrogen receptor signaling pathway | 1 |
| response to estradiol | 1 |
Indications & clinical
Indications
5 indications (0 at ChEMBL trial phase 4). Phase below is the highest clinical-trial phase recorded for this drug against each disease — not the molecule’s overall approval status (that is in the Summary).
| Indication | Trial phase | MONDO | EFO |
|---|---|---|---|
| osteoporosis | 3 | MONDO:0005298 | EFO:0003882 |
| physiological sexual disorder | 3 | MONDO:0002134 | EFO:0004714 |
| breast neoplasm | 3 | MONDO:0021100 | MONDO:0007254 |
| major depressive disorder | 1 | MONDO:0002009 | MONDO:0002009 |
1 further indication record had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.
Clinical trials
Total trials: 21.
Phase distribution
| Phase | Trials |
|---|---|
| PHASE4 | 10 |
| PHASE3 | 5 |
| Not specified | 4 |
| PHASE2 | 1 |
| PHASE1 | 1 |
Top trials by phase / activity
| NCT | Phase | Status | Title |
|---|---|---|---|
| NCT00145522 | PHASE4 | COMPLETED | Study to Compare the Effect of Hormone Replacement Therapy (HRT) on Breast and Cardiovascular Metabolic Markers in Postmenopausal Women |
| NCT00294463 | PHASE4 | COMPLETED | Effects of Tibolone Treatment on the Endometrium |
| NCT00431093 | PHASE4 | COMPLETED | Trial to Compare the Effects of Tibolone (Livial®) and Continuous Combined Low-Dose Estradiol/Noresterone (Activelle®) |
| NCT00431431 | PHASE4 | COMPLETED | Comparison of Tibolone and Raloxifene on Bone Mineral Density in Osteopenic Postmenopausal Women (P06090) |
| NCT00472004 | PHASE4 | COMPLETED | Study Comparing 17B Estradiol/TMG CC 1mg Vs. Tibolone In Postmenopausal Women |
| NCT00809068 | PHASE4 | COMPLETED | High-density Lipoprotein (HDL) Cholesterol in Women Taking Tibolone |
| NCT01368068 | PHASE4 | TERMINATED | Investigation of Tibolone and Escitalopram in Perimenopausal Depression |
| NCT01470092 | PHASE4 | COMPLETED | Tibolone and Placebo in Adjunct to Antidepressant Medication for Women With Menopausal Depression |
| NCT01822288 | PHASE4 | COMPLETED | The Impact of Hormone Therapy on Lower Urinary Tract Symptoms, Sexual Function and Psychosomatic Disorder |
| NCT06117969 | PHASE4 | UNKNOWN | the Effects of Different Therapy Regimens on Menopausal Sleep Disorders |
| NCT00408863 | PHASE3 | COMPLETED | Livial Intervention Following Breast Cancer; Efficacy, Recurrence and Tolerability Endpoints (LIBERATE)(COMPLETED)(P05885) |
| NCT00413764 | PHASE3 | COMPLETED | Efficacy of Tibolone Versus Transdermal E2/NETA on Sexual Function in Naturally Postmenopausal Women (P06089) |
| NCT00519857 | PHASE3 | COMPLETED | Trial to Evaluate Tibolone in the Treatment of Osteoporosis (P06468) |
| NCT00725374 | PHASE3 | COMPLETED | A Study to Investigate the Effects of Tibolone (Livial®) on Breast Tissue in Postmenopausal Women With Breast Cancer (Study 32971)(P06469) |
| NCT00745108 | PHASE3 | COMPLETED | Tibolone Endometrium Study (Study 32972)(P06470) |
| NCT00165204 | PHASE2 | COMPLETED | Effects of Tibilone on Bone Density, Menopause Symptoms and Breast Density in Women After Prophylactic Oophorectomy |
| NCT01239888 | PHASE1 | UNKNOWN | Oxytocin and Tibolone Adjuncts in Treatment Resistant Depression - A Pilot Study |
| NCT05280028 | Not specified | RECRUITING | HRT on Overactive Bladder Symptoms, Sexual Function, Depressive Symptoms, Autonomic Function, and Arterial Stiffness |
| NCT01543399 | Not specified | COMPLETED | Vascular Effect of Tibolone in the Brachial Artery |
| NCT01679795 | Not specified | COMPLETED | Vascular Effect of Tibolone Versus Placebo Evaluated by Flow-mediated Dilatation of Brachial Artery |
| NCT05846698 | Not specified | COMPLETED | The Effects of Luo-Bu-Fu-Ke-Bi-RI Pill |
Clinical evidence (CIViC)
No CIViC predictive evidence (expected for non-precision-medicine drugs).
Pharmacology
Pharmacogenomics
No PharmGKB pharmacogenomic data curated for this drug.
Related molecules
Related molecules
Molecules sharing ≥1 of this drug’s curated primary targets, merged from two biobtree sources and ranked by shared-target count, then clinical phase: ChEMBL clinical-stage candidates (development phase ≥2) and PubChem drug-class bioactivity (approved / known drugs acting on the target). Deduplicated by drug name; the drug’s own salt forms are excluded. Note: for a drug with few primary targets a shared-target match can reflect off-target / promiscuous binding rather than the same therapeutic mechanism — the phase ordering surfaces bona-fide therapeutics first.
173 molecules share ≥1 primary target. Top 60 by shared-target count:
| Molecule | Source | Status | Shared targets |
|---|---|---|---|
| FULVESTRANT | ChEMBL + PubChem | Phase 4 (approved) | ESR1 |
| ACETOPHENAZINE | ChEMBL | Phase 4 (approved) | ESR1 |
| ALECTINIB | ChEMBL | Phase 4 (approved) | ESR1 |
| APOMORPHINE | ChEMBL | Phase 4 (approved) | ESR1 |
| ARIPIPRAZOLE | ChEMBL | Phase 4 (approved) | ESR1 |
| ASPIRIN | ChEMBL | Phase 4 (approved) | ESR1 |
| AZTREONAM | ChEMBL | Phase 4 (approved) | ESR1 |
| BAZEDOXIFENE | ChEMBL | Phase 4 (approved) | ESR1 |
| BELINOSTAT | ChEMBL | Phase 4 (approved) | ESR1 |
| BENZBROMARONE | ChEMBL | Phase 4 (approved) | ESR1 |
| BEXAROTENE | ChEMBL | Phase 4 (approved) | ESR1 |
| BISACODYL | ChEMBL | Phase 4 (approved) | ESR1 |
| BITHIONOL | ChEMBL | Phase 4 (approved) | ESR1 |
| BROMOCRIPTINE | ChEMBL | Phase 4 (approved) | ESR1 |
| BUTOCONAZOLE | ChEMBL | Phase 4 (approved) | ESR1 |
| CANDESARTAN CILEXETIL | ChEMBL | Phase 4 (approved) | ESR1 |
| CASPOFUNGIN | ChEMBL | Phase 4 (approved) | ESR1 |
| CEFADROXIL | ChEMBL | Phase 4 (approved) | ESR1 |
| CEFEPIME | ChEMBL | Phase 4 (approved) | ESR1 |
| CEFTAZIDIME | ChEMBL | Phase 4 (approved) | ESR1 |
| CERIVASTATIN | ChEMBL | Phase 4 (approved) | ESR1 |
| CHLOROTRIANISENE | ChEMBL | Phase 4 (approved) | ESR1 |
| CISPLATIN | ChEMBL | Phase 4 (approved) | ESR1 |
| CLOFAZIMINE | ChEMBL | Phase 4 (approved) | ESR1 |
| CLOMIPHENE | ChEMBL | Phase 4 (approved) | ESR1 |
| CYCLOFENIL | ChEMBL | Phase 4 (approved) | ESR1 |
| DANAZOL | ChEMBL | Phase 4 (approved) | ESR1 |
| DAUNORUBICIN | ChEMBL | Phase 4 (approved) | ESR1 |
| DEQUALINIUM | ChEMBL | Phase 4 (approved) | ESR1 |
| DESOGESTREL | ChEMBL | Phase 4 (approved) | ESR1 |
| DIENESTROL | ChEMBL | Phase 4 (approved) | ESR1 |
| DIETHYLSTILBESTROL | ChEMBL | Phase 4 (approved) | ESR1 |
| DINOPROSTONE | ChEMBL | Phase 4 (approved) | ESR1 |
| DOXORUBICIN | ChEMBL | Phase 4 (approved) | ESR1 |
| DRONEDARONE | ChEMBL | Phase 4 (approved) | ESR1 |
| ELACESTRANT | ChEMBL | Phase 4 (approved) | ESR1 |
| ERGOCALCIFEROL | ChEMBL | Phase 4 (approved) | ESR1 |
| ERTAPENEM | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTETROL | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRADIOL | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRADIOL CYPIONATE | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRADIOL VALERATE | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRAMUSTINE | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRIOL | ChEMBL | Phase 4 (approved) | ESR1 |
| ESTRONE | ChEMBL | Phase 4 (approved) | ESR1 |
| ETHINYL ESTRADIOL | ChEMBL | Phase 4 (approved) | ESR1 |
| ETHYLESTRENOL | ChEMBL | Phase 4 (approved) | ESR1 |
| ETHYNODIOL DIACETATE | ChEMBL | Phase 4 (approved) | ESR1 |
| ETONOGESTREL | ChEMBL | Phase 4 (approved) | ESR1 |
| ETRAVIRINE | ChEMBL | Phase 4 (approved) | ESR1 |
| FLUPIRTINE | ChEMBL | Phase 4 (approved) | ESR1 |
| HEXACHLOROPHENE | ChEMBL | Phase 4 (approved) | ESR1 |
| HEXESTROL | ChEMBL | Phase 4 (approved) | ESR1 |
| IBUPROFEN | ChEMBL | Phase 4 (approved) | ESR1 |
| ISOCONAZOLE | ChEMBL | Phase 4 (approved) | ESR1 |
| LASOFOXIFENE | ChEMBL | Phase 4 (approved) | ESR1 |
| LENVATINIB | ChEMBL | Phase 4 (approved) | ESR1 |
| LEVONORGESTREL | ChEMBL | Phase 4 (approved) | ESR1 |
| LUSUTROMBOPAG | ChEMBL | Phase 4 (approved) | ESR1 |
| LYMECYCLINE | ChEMBL | Phase 4 (approved) | ESR1 |
Related Atlas pages
- Genes: ESR1
- Diseases: osteoporosis, physiological sexual disorder, breast neoplasm
- Drugs: Fulvestrant, Acetophenazine, Alectinib, Apomorphine, Aripiprazole, Aspirin, Aztreonam, Bazedoxifene, Belinostat, Benzbromarone, Bexarotene, Bisacodyl, Bithionol, Bromocriptine, Butoconazole, Candesartan Cilexetil, Caspofungin, Cefadroxil, Cefepime, Ceftazidime, Cerivastatin, Chlorotrianisene, Cisplatin, Clofazimine, Clomiphene, Cyclofenil, Danazol, Daunorubicin, Dequalinium, Desogestrel, Dienestrol, Diethylstilbestrol, Dinoprostone, Doxorubicin, Dronedarone, Elacestrant, Ergocalciferol, Ertapenem, Estetrol, Estradiol, Estradiol Cypionate, Estradiol Valerate, Estramustine, Estriol, Estrone, Ethinyl Estradiol, Ethylestrenol, Ethynodiol Diacetate, Etonogestrel, Etravirine, Flupirtine, Hexachlorophene, Hexestrol, Ibuprofen, Isoconazole, Lasofoxifene, Lenvatinib, Levonorgestrel, Lusutrombopag, Lymecycline