Estradiol

Summary

Estradiol (CHEMBL135) is an approved small-molecule EC 1.2.3.1 (aldehyde oxidase) inhibitor (ATC G03CA03) targeting GPER1; indicated across 55 conditions including breast carcinoma and osteoporosis.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: G03CA03
• Targets: 1 (GPER1)
• Indications: 55 conditions
• Clinical trials: 323
• Chemistry: 272.4 Da · C18H24O2

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL135
Name	Estradiol
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	5757
ChEBI	CHEBI:16469
ATC	G03CA03
Molecular formula	C18H24O2
Molecular weight	272.4
InChIKey	VOXZDWNPVJITMN-ZBRFXRBCSA-N

SMILES: C[C@]12CC[C@H]3[C@H]([C@@H]1CC[C@@H]2O)CCC4=C3C=CC(=C4)O

IUPAC name: (8R,9S,13S,14S,17S)-13-methyl-6,7,8,9,11,12,14,15,16,17-decahydrocyclopenta[a]phenanthrene-3,17-diol

ChEBI definition: The 17β-isomer of estradiol.

Pharmacological roles (ChEBI): estrogen, EC 1.2.3.1 (aldehyde oxidase) inhibitor, geroprotector.

Other ChEBI roles (chemical / environmental): human metabolite, Daphnia magna metabolite, mouse metabolite.

Also known as: 17 .beta.-estradiol, 17.beta.-estradiol, 17beta-estradiol, Adgyn estro, Aerodiol, Alora, Aquagen, Bedol, Climara, Dermestril 100, Dermestril 25, Dermestril 50

Patent coverage: 40,093 distinct patent families (123,080 SureChEMBL compound mentions), from 2 matched compound structure(s). One matched structure accounts for 121,588 (99%) of the total. 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
GPER1	GPER	Full agonist	8.6	0.2%	Q99527

Broader ChEMBL bioactivity targets: 50 (assay-derived). Sample: Microtubule-associated protein tau, Survival motor neuron protein, Prelamin-A/C, ATP-dependent DNA helicase Q1, RecQ-like DNA helicase BLM, Peripheral myelin protein 22, Aldehyde oxidase 1, Aldehyde oxidase 1, Aldehyde oxidase 1, Sulfotransferase 1A1.

Bioactivity

ChEMBL activities: 374 potent at pChembl ≥ 5 of 400 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ESR1	11.34	ED50	0	nM	CHEMBL_ACT_1142204
ESR1	11	EC50	0.01	nM	CHEMBL_ACT_1157507
ESR2	11	EC50	0.01	nM	CHEMBL_ACT_12158357
ESR1	11	EC50	0.01	nM	CHEMBL_ACT_1661250
ESR1	11	IC50	0.01	nM	CHEMBL_ACT_459335
ESR2	10.82	Ki	0.01	nM	CHEMBL_ACT_16312210
ESR2	10.82	Ki	0.01	nM	CHEMBL_ACT_16326890
ESR2	10.82	Ki	0.01	nM	CHEMBL_ACT_26595854
ESR2	10.82	Ki	0.01	nM	CHEMBL_ACT_26596481
ESR2	10.82	Ki	0.01	nM	CHEMBL_ACT_26768809
ESR1	10.74	EC50	0.02	nM	CHEMBL_ACT_782678
ESR1	10.72	EC50	0.02	nM	CHEMBL_ACT_1608716
ESR2	10.7	EC50	0.02	nM	CHEMBL_ACT_19212896
ESR1	10.7	EC50	0.02	nM	CHEMBL_ACT_200449
ESR2	10.66	EC50	0.02	nM	CHEMBL_ACT_18749207
ESR2	10.66	EC50	0.02	nM	CHEMBL_ACT_19114241
ESR2	10.66	EC50	0.02	nM	CHEMBL_ACT_22894630
ESR2	10.66	EC50	0.02	nM	CHEMBL_ACT_24691942
ESR1	10.52	EC50	0.03	nM	CHEMBL_ACT_1149533
ESR1	10.52	EC50	0.03	nM	CHEMBL_ACT_18706884
ESR2	10.44	EC50	0.04	nM	CHEMBL_ACT_10985995
ESR2	10.41	EC50	0.04	nM	CHEMBL_ACT_782679
ESR2	10.4	EC50	0.04	nM	CHEMBL_ACT_13965790
ESR2	10.4	EC50	0.04	nM	CHEMBL_ACT_22837882
ESR2	10.34	IC50	0.05	nM	CHEMBL_ACT_13867399
ESR1	10.34	EC50	0.05	nM	CHEMBL_ACT_6374180
ESR1	10.33	EC50	0.05	nM	CHEMBL_ACT_2429824
P06211	10.22	ED50	0.06	nM	CHEMBL_ACT_1487710
ESR2	10.21	EC50	0.06	nM	CHEMBL_ACT_3285752
ESR1	10.19	EC50	0.06	nM	CHEMBL_ACT_3285726

Target pathways

Aggregated over 1 target gene(s): GPER1.

Top Reactome pathways

3 total, by targets touching each:

Pathway	Targets	Genes
Peptide ligand-binding receptors	1	GPER1
G alpha (i) signalling events	1	GPER1
GPER1 signaling	1	GPER1

Dominant GO biological processes

GO term	Targets
positive regulation of protein phosphorylation	1
positive regulation of neurotransmitter secretion	1
negative regulation of leukocyte activation	1
inflammatory response	1
G protein-coupled receptor signaling pathway	1
adenylate cyclase-activating G protein-coupled receptor signaling pathway	1
positive regulation of cytosolic calcium ion concentration	1
nervous system development	1
positive regulation of cell population proliferation	1
negative regulation of cell population proliferation	1
positive regulation of gene expression	1
negative regulation of gene expression	1
negative regulation of cell cycle process	1
neuronal action potential	1
cell differentiation	1

Indications & clinical

Indications

55 indications (13 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
breast carcinoma	4	MONDO:0004989	EFO:0000305
osteoporosis	4	MONDO:0005298	EFO:0003882
breast neoplasm	4	MONDO:0021100	EFO:0003869
postmenopausal atrophic vaginitis	4	MONDO:0001410	EFO:1001271
primary ovarian failure	4	MONDO:0005387	HP:0008209
psychologic dyspareunia	4	MONDO:0001196	HP:0030016
hypogonadism	4	MONDO:0002146	MONDO:0002146
postmenopausal osteoporosis	4	MONDO:0008159	EFO:0003854
physiological sexual disorder	3	MONDO:0002134	EFO:0004714
infertility disorder	3	MONDO:0005047	EFO:0000545
endometriosis	3	MONDO:0005133	EFO:0001065
obesity disorder	3	MONDO:0011122	EFO:0001073
post-traumatic stress disorder	3	MONDO:0005146	EFO:0001358
amenorrhea	3	MONDO:0001836	EFO:0010269
myocardial ischemia	3	MONDO:0024644	EFO:1001375
metabolic dysfunction-associated steatohepatitis	3	MONDO:0007027	EFO:1001249
multiple sclerosis	3	MONDO:0005301	MONDO:0005301
Turner syndrome	3	MONDO:0019499	MONDO:0019499
anorexia nervosa	3	MONDO:0005351	MONDO:0005351
coronary artery disorder	3	MONDO:0005010	EFO:0001645
heart disorder	3	MONDO:0005267	EFO:0003777
HIV infectious disease	2	MONDO:0005109	EFO:0000764
prostate carcinoma	2	MONDO:0005159	EFO:0001663
atherosclerosis	2	MONDO:0005311	EFO:0003914
postpartum depression	2	MONDO:0005929	EFO:0007453
carcinoid tumor	2	MONDO:0005369	EFO:0004243
schizoaffective disorder	2	MONDO:0005487	EFO:0005411
hereditary breast ovarian cancer syndrome	2	MONDO:0003582	Orphanet:145
dry eye syndrome	2	MONDO:0006733	EFO:1000906
bulimia nervosa	2	MONDO:0005452	EFO:0005204
depressive disorder	2	MONDO:0002050	MONDO:0002050
severe acute respiratory syndrome	2	MONDO:0005091	MONDO:0100096
urinary tract infection	2	MONDO:0100338	EFO:0003103
Alzheimer disease	2	MONDO:0004975	MONDO:0004975
migraine disorder	2	MONDO:0005277	MONDO:0005277
triple-negative breast carcinoma	2	MONDO:0005494	EFO:0005537
polycystic ovary syndrome	1	MONDO:0008487	EFO:0000660
type 1 diabetes mellitus	1	MONDO:0005147	MONDO:0005147
type 2 diabetes mellitus	1	MONDO:0005148	MONDO:0005148
diabetes mellitus	1	MONDO:0005015	EFO:0000400
cerebral arterial disease	0	MONDO:0006693	EFO:1000859
blood coagulation disease	0	MONDO:0001531	EFO:0009314

13 further indication records had no mapped disease name (EFO/MeSH-only) or were duplicates, and are omitted.

Clinical trials

Total trials: 323.

Phase distribution

Phase	Trials
Not specified	87
PHASE4	68
PHASE3	62
PHASE2	61
PHASE1	17
EARLY_PHASE1	12
PHASE2/PHASE3	9
PHASE1/PHASE2	7

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05221021	PHASE4	RECRUITING	Vaginal Estradiol vs Oral Beta-3 Agonist for Overactive Bladder Syndrome
NCT05282277	PHASE4	RECRUITING	Examining the Effects of Estradiol on Neural and Molecular Response to Reward
NCT05457972	PHASE4	RECRUITING	Postpartum Vaginal Estrogen for Breastfeeding Patients
NCT05562518	PHASE4	ACTIVE_NOT_RECRUITING	GRACE-trial: a Randomized Active-controlled Trial for vulvovaGinal atRophy in breAst Cancer Patients on Endocrine Therapy.
NCT05663892	PHASE4	ACTIVE_NOT_RECRUITING	Drug-Drug Interaction Study in Trans Women Living With HIV
NCT05704036	PHASE4	RECRUITING	Estrogen Supplementation and Bone Health in Women With CF
NCT06264882	PHASE4	RECRUITING	Cardiometabolic Consequences of the Loss of Ovarian Function
NCT06353269	PHASE4	ACTIVE_NOT_RECRUITING	Adherence to Vaginal Estrogen Therapy in Hypoestrogenic Women With Recurrent Urinary Tract Infections
NCT06455969	PHASE4	RECRUITING	Adaptions and Resiliency to Multi-Stressor OpeRations
NCT06544473	PHASE4	RECRUITING	Determining Dose Equivalence Between Oral and Transdermal Estrogen Treatment in Women With Turner Syndrome
NCT06570460	PHASE4	RECRUITING	Long Term Effects of Oral Versus Transdermal Estrogen Replacement Therapy in Turner Syndrome
NCT06610305	PHASE4	RECRUITING	Ovarian Hormone Withdrawal, Anhedonia, and Reward Sensitivity in Women With Premenstrual Exacerbations of Depression
NCT06798571	PHASE4	RECRUITING	Role of Menopause in Thermoregulation
NCT06896617	PHASE4	RECRUITING	Impact of the Presence of the Corpus Luteum on Pregnancies Obtained Through Frozen Embryo Transfer(FET)
NCT07160504	PHASE4	RECRUITING	Vaginal Estrogen Treatment and Effect on Hemostatic Parameters in Postmenopausal Women
NCT07420218	PHASE4	NOT_YET_RECRUITING	Menopausal Hormones and Sympathetic Activation
NCT07526948	PHASE4	NOT_YET_RECRUITING	Vaginal Estradiol vs Moisturizer to Improve Postmenopausal Vaginal Aging Symptoms and the Microbiome in Women Living With HIV
NCT00030147	PHASE4	COMPLETED	Raloxifene and Rimostil for Perimenopause-Related Depression
NCT00134745	PHASE4	COMPLETED	Defining the Optimal Hormonal Replacement Therapy in Turner Syndrome
NCT00160173	PHASE4	COMPLETED	Efficacy Study Comparing 0.9 g and 1.25 g Estrogel With Placebo for Vasomotor Symptoms and Vulvar and Vaginal Atrophy
NCT00185328	PHASE4	COMPLETED	Efficacy and Tolerability of Angeliq in Thai Women
NCT00229450	PHASE4	COMPLETED	Estrogen and Perimenopausal Depression
NCT00294463	PHASE4	COMPLETED	Effects of Tibolone Treatment on the Endometrium
NCT00732693	PHASE4	COMPLETED	Evaluation of Physiologic and Standard Sex Steroid Replacement Regimens in Women With Premature Ovarian Failure
NCT00744328	PHASE4	TERMINATED	Postpartum Depression: Transdermal Estradiol Versus Sertraline
NCT01065220	PHASE4	COMPLETED	Sex Steroids and the Serotonin Transporter
NCT01109979	PHASE4	COMPLETED	Effect of Estradiol+Drospirenone Versus Estradiol+MPA on Endothelial Function
NCT01165307	PHASE4	COMPLETED	Medical Therapy Versus Radiofrequency Endometrial Ablation in the Initial Treatment of Menorrhagia
NCT01295892	PHASE4	COMPLETED	Chronic Effects of Estrogen in Microcirculation
NCT01489852	PHASE4	COMPLETED	Estrogen Pretreatment Prior to GnRH Antagonist Protocol
NCT01668446	PHASE4	COMPLETED	Effect of Adding Sildenafil to Protocol of Endometrial Preparation in Outcome of Frozen-thawed Embryo Transfer Cycles
NCT01705249	PHASE4	COMPLETED	Bleeding Profile With Continuous Hormone Replacement Therapy of Activelle® in Postmenopausal Women
NCT01822288	PHASE4	COMPLETED	The Impact of Hormone Therapy on Lower Urinary Tract Symptoms, Sexual Function and Psychosomatic Disorder
NCT01833663	PHASE4	COMPLETED	Effectiveness and Safety Study of Solifenacin Succinate and Solifenacin Succinate + Estrogen to Treat OAB in Postmenopausal Women
NCT01943812	PHASE4	COMPLETED	Substituted Frozen Embryo Transfer Cycles With GnRH-agonist Supplementation
NCT01958073	PHASE4	COMPLETED	Vaginal Estrogen for the Prevention of Recurrent Urinary Tract Infection in Postmenopausal Women
NCT01980680	PHASE4	COMPLETED	The Exogenous Progesterone Free Luteal Phase After GnRHa Trigger - a Pilot Study in Normo-responder IVF Patients
NCT02186782	PHASE4	UNKNOWN	Concomitant CC and E2 Versus CC Alone in Ovulation Induction
NCT02255175	PHASE4	COMPLETED	Perimenopausal Effects of Estradiol on Reward Responsiveness
NCT02427386	PHASE4	COMPLETED	Homeopathic Treatment of Chronic Pelvic Pain in Women With Endometriosis

Clinical evidence (CIViC)

No CIViC predictive evidence (expected for non-precision-medicine drugs).

Pharmacology

Pharmacogenomics

No CPIC/DPWG dosing guideline, but PharmGKB curates 1 clinical and 24 variant annotation(s) for this drug (gene-keyed; see PharmGKB).

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.

3 molecules share ≥1 primary target. Top 3 by shared-target count:

Molecule	Source	Status	Shared targets
Fulvestrant	PubChem	Approved	GPER1
Raloxifene	PubChem	Approved	GPER1
Tamoxifen	PubChem	Approved	GPER1