Clomiphene

Summary

Clomiphene (CHEMBL2355051) is an approved small-molecule estrogen antagonist (ATC G03GB02) targeting ESR1; indicated across 3 conditions including hypogonadism and anovulation.

At a glance

• Status: Approved (max clinical phase 4)
• Modality: Small molecule
• ATC class: G03GB02
• Targets: 1 (ESR1)
• Indications: 3 conditions
• Clinical trials: 115
• Chemistry: 406 Da · C26H28ClNO

Identifiers

Drug identity and classification

Field	Value
ChEMBL ID	CHEMBL2355051
Name	Clomiphene
Type	Small molecule
Max phase	4
FDA approved	yes
PubChem CID	2800
ChEBI	CHEBI:3752
ATC	G03GB02
Molecular formula	C26H28ClNO
Molecular weight	406
InChIKey	GKIRPKYJQBWNGO-UHFFFAOYSA-N

SMILES: CCN(CC)CCOC1=CC=C(C=C1)C(=C(C2=CC=CC=C2)Cl)C3=CC=CC=C3

IUPAC name: 2-[4-(2-chloro-1,2-diphenylethenyl)phenoxy]-N,N-diethylethanamine

Pharmacological roles (ChEBI): estrogen antagonist, estrogen receptor modulator.

Also known as: Clomifene, Clomifeno, Clomiphene, Clomiphene citrate, SID11532948, Clomiphene Citrate, clomiphene citrate, SID144206661, CLOMIPHENE CITRATE, CLOMIFENE, SID144212192, SID170464951

Parent form; salt/anhydrous children: CHEMBL3185958

Patent coverage: 25 distinct patent families (36 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	Antagonist	8.89	1.7%	P03372
	VRAC

Broader ChEMBL bioactivity targets: 31 (assay-derived). Sample: Microtubule-associated protein tau, Lysine-specific demethylase 4E, Nuclear receptor ROR-gamma, Ferritin light chain, Protein RecA, Replicative DNA helicase DnaB, NACHT, LRR and PYD domains-containing protein 3, Alpha-2A adrenergic receptor, Androgen receptor, D(1A) dopamine receptor.

Bioactivity

ChEMBL activities: 22 potent at pChembl ≥ 5 of 35 total. Top 30 by potency (10 = 0.1 nM, 6 = 1 µM):

Target	pChembl	Type	Value	Unit	Activity ID
ESR1	8.48	AC50	3.3	nM	CHEMBL_ACT_25139464
PTGS1	7.18	AC50	66.1	nM	CHEMBL_ACT_25205830
DRD3	6.45	AC50	357.3	nM	CHEMBL_ACT_25195110
AR	6.25	AC50	565.8	nM	CHEMBL_ACT_25203964
KCNH2	6.1	AC50	800	nM	CHEMBL_ACT_25118851
SLC6A3	6.03	AC50	928.8	nM	CHEMBL_ACT_25125565
SLC6A2	5.89	AC50	1295	nM	CHEMBL_ACT_25146606
PGR	5.86	AC50	1388	nM	CHEMBL_ACT_25204897
HTR6	5.71	Ki	1956	nM	CHEMBL_ACT_12059575
ADORA3	5.62	AC50	2381	nM	CHEMBL_ACT_25199207
NLRP3	5.62	IC50	2410	nM	CHEMBL_ACT_5562661
CHRM2	5.52	AC50	3023	nM	CHEMBL_ACT_25196342
ADRA2A	5.4	AC50	3972	nM	CHEMBL_ACT_25157035
DRD1	5.38	AC50	4156	nM	CHEMBL_ACT_25115816
P9WMR3	5.36	AC50	4342	nM	CHEMBL_ACT_6543906
SLC6A4	5.32	AC50	4846	nM	CHEMBL_ACT_25151933
HTR1A	5.26	AC50	5461	nM	CHEMBL_ACT_25165630
CHRM1	5.25	AC50	5600	nM	CHEMBL_ACT_25210741
MEN1	5.2	Potency	6310	nM	CHEMBL_ACT_4539275
PDE4A	5.16	AC50	6857	nM	CHEMBL_ACT_25207693
P9WMR3	5.03	AC50	9307	nM	CHEMBL_ACT_7198770
NPSR1	5	Potency	10000	nM	CHEMBL_ACT_4912530

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

3 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
hypogonadism	2	MONDO:0002146	MONDO:0002146
anovulation	1	MONDO:0002775	MONDO:0002775

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

Clinical trials

Total trials: 115.

Phase distribution

Phase	Trials
PHASE4	39
Not specified	30
PHASE2	19
PHASE3	12
PHASE2/PHASE3	8
PHASE1	4
EARLY_PHASE1	2
PHASE1/PHASE2	1

Top trials by phase / activity

NCT	Phase	Status	Title
NCT05206448	PHASE4	ACTIVE_NOT_RECRUITING	Randomized Controlled Trial of Combined Letrozole and Clomid (CLC II) Versus Letrozole Alone for Women With Anovulation
NCT06701071	PHASE4	RECRUITING	Evaluation of a Long Versus Short Clomid Protocol for Controlled Ovarian Stimulation
NCT07462065	PHASE4	RECRUITING	Effect Clomiphene vs Clomiphene Along With Pioglitazone on Ovarian Stimulation Rate
NCT07523022	PHASE4	ENROLLING_BY_INVITATION	Comparison of the Effect of Gonadotropin and Clomiphene Citrate Treatment on Sperm Parameters and the Outcome of Assisted Reproductive Procedures in Subfertile Men Based on the APHRODITE Groups
NCT00461643	PHASE4	UNKNOWN	Strategies for Ovulation Induction in Anovulatory Infertile Patients With PCOS
NCT00471523	PHASE4	COMPLETED	Treatment of Anovulatory Infertility in PCOS Patients
NCT00478504	PHASE4	COMPLETED	Letrozole Versus Clomifene Citrate for Ovulation Induction
NCT00501839	PHASE4	WITHDRAWN	Clomiphene Citrate in Infertile PCOS Patients
NCT00502229	PHASE4	WITHDRAWN	Therapy for Infertile PCOS Patients Ovulating Under Clomiphene Citrate or Metformin
NCT00795808	PHASE4	COMPLETED	PCOSMIC Trial - PolyCystic Ovary Syndrome, Metformin for Infertility With Clomiphene
NCT00830492	PHASE4	COMPLETED	Clomiphene Citrate (CC)/Gonadotropin/Gonadotropin Releasing Hormone (GnRH) Antagonist Versus Gonadotropin/GnRH Agonist
NCT00835744	PHASE4	COMPLETED	Comparison of Clomiphene Citrate and Gonadotropins in Ovulation Induction Cycles
NCT01004068	PHASE4	COMPLETED	Short-term Structured Exercise Training Program Plus Diet Intervention in Patients With Polycystic Ovary Syndrome (PCOS)
NCT01213147	PHASE4	COMPLETED	Mild Stimulation Protocol Versus Microdose Gonadotropin-releasing Hormone Agonist Flare up Protocol in Poor Responders
NCT01529177	PHASE4	UNKNOWN	Metformin for the Treatment of Unexplained Oligozspermia
NCT01577199	PHASE4	WITHDRAWN	RCT of Low-dose Clomiphene vs. High Dose Gonadotropin Protocol for IVF Poor Responders
NCT01791751	PHASE4	COMPLETED	Impact of Clomiphene Citrate Administration During the Early Luteal Phase on Endocrine Profile in IVF Cycles
NCT02186782	PHASE4	UNKNOWN	Concomitant CC and E2 Versus CC Alone in Ovulation Induction
NCT02201914	PHASE4	UNKNOWN	Clomiphene Citrate Plus Gonadotropins and GnRH Antagonist Versus Flexible GnRH Antagonist Protocol Versus Microdose GnRH Agonist Protocol in Poor Responders Undergoing IVF
NCT02344888	PHASE4	UNKNOWN	Adding Prednisolone During Ovulation Induction With CC in Lean Women With CC Resistant PCOS
NCT02352597	PHASE4	COMPLETED	Phytoestrogens as an Alternative to Estradiol in Ovulation Induction in PCOS
NCT02436226	PHASE4	COMPLETED	Use of Low Dose of HCG During Ovulation Induction With CC in Women With CC Resistant PCOS
NCT02479256	PHASE4	COMPLETED	Clomiphene Citrate Versus Tamoxifen for Ovulation Induction in PCOs
NCT02575248	PHASE4	UNKNOWN	Induction of Ovulation by Clomiphene Citrate Following Laparoscopic Surgery for Endometriosis Stage 1 and Stage 2 With and Without Suppression by Dienogest
NCT02638285	PHASE4	COMPLETED	Pregnancy Rate by HCG Administration Versus Urinary LH Surge Method in Patients Undergoing IUI
NCT02690870	PHASE4	UNKNOWN	Tamoxifen and Clomiphene Citrate in Mild Stimulation IVF
NCT02802865	PHASE4	COMPLETED	Combined Letrozole and Clomid in Women With Infertility and PCOS
NCT02890238	PHASE4	UNKNOWN	Sildenafil Effect After Ovulation Induction
NCT03400722	PHASE4	UNKNOWN	Double Ovarian Stimulation as Accumulation Strategy for Older Infertile Patients With Suboptimal Ovarian Response
NCT03630341	PHASE4	COMPLETED	Adding L-Carnitine to Clomiphene Citrate for Induction of Ovulation in Women With Polycystic Ovary Syndrome
NCT03806036	PHASE4	UNKNOWN	The Effect Of Vitamin D Replacement Therapy On Serum Leptin And Follicular Growth Pattern In Women With Resistant Polycystic Ovary
NCT03989024	PHASE4	UNKNOWN	Pulsatile Gonadotropin-releasing Hormone for Infertility in Non-obese Patients With Polycystic Ovary Syndrome
NCT04010942	PHASE4	COMPLETED	Vitamin D for Polycystic Ovary Syndrome Clomiphene Resistant Women
NCT04210765	PHASE4	COMPLETED	Incremental Clomiphene Citrate Doses in Successive Cycles and FSH, LH and Steroid Hormone Levels
NCT04302532	PHASE4	COMPLETED	Coenzyme q 10 and Fertility Outcome in Women With Clomiphene Resistant PCOS
NCT04306692	PHASE4	TERMINATED	Myo-inositol Versus Clomiphene Citrate in PCOS
NCT04331197	PHASE4	UNKNOWN	BMI Effect on the Response to Ovulation Induction in Letrozole vs Clomid
NCT05753098	PHASE4	COMPLETED	Effect of Sildenafil Citrate Compared to Estrogen as Adjuvant Therapy for Unexplained Infertility
NCT06178523	PHASE4	COMPLETED	Cost-effective Treatment of Unexplained Infertility
NCT03059173	PHASE3	RECRUITING	Interest of Myo-inositol Supplementation in Women With Polycystic Ovarian Syndrome

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
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
MASOPROCOL	ChEMBL	Phase 4 (approved)	ESR1